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Antifungal susceptibility, genotyping, resistance mechanism, and clinical profile of Candida tropicalis blood isolates - myz124_supplement_tables

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Oligo Name Sequence Target gene/Purpose PCR product sizes Reference

Ct-ERG11-Fexternal TTCTCCCATTGTACACTA

CtERG11/PCR and sequencing 2186bps This study

Ct-ERG11-F1 CATGGTTTGGTTCTGCTG CtERG11/Sequencing --- This study

Ct-ERG11-F2 TCGACAGATCATTTGCTCA CtERG11/Sequencing --- This study

Ct-ERG11-F3 GAGAATGCACATGCCATT CtERG11/Sequencing --- This study

Ct-ERG11-R1 GAATTCGTGACCTTTT CtERG11/Sequencing --- This study

Ct-ERG11-R2 TTTCTTTGAGCAGCGTCA CtERG11/Sequencing --- This study

Ct-ERG11-R3 GAAATGTTCTGGGTGTTCA CtERG11/Sequencing --- This study

Ct-ERG11-Rexternal TACATCCAAATAATGGGC CtERG11/PCR and sequencing 2186bps This study

Ct-UPC2-1-Fexternal ACCATCATCATTATAGCC CtUPC2/PCR and sequencing 2647bps This study

Ct-UPC2-F1 TGTCAAATGTGATGAACA CtUPC2/Sequencing --- This study

Ct-UPC2-F2 ACAATCTTGCTGCAAC CtUPC2/Sequencing --- This study

Ct-UPC2-F3 GATTCTATAAGTTCATTTCAG CtUPC2/Sequencing --- This study

Ct-UPC2-R1 AGATACTGCCAGTGATT CtUPC2/Sequencing --- This study

Ct-UPC2-R2 CAAATCAAGCATATTAAGAC CtUPC2/Sequencing

Ct-UPC2-R3 TAAGAAGCTCCTTCAC CtUPC2/Sequencing

Ct-UPC2-R4 TATCTCCTTGCATGATA CtUPC2/Sequencing

Ct-UPC2-Rexternal. CTAGTATCCACACTTATCTC CtUPC2/PCR and sequencing 2647bps This study

Ct-MRR1-Fexternal ATCAATCATCAAGTACCC CtMRR1/PCR and sequencing 3639bps This study

Ct-MRR1-F1 CATCAGTGAACTATGATAA CtMRR1/ Sequencing --- This study

Ct-MRR1-F2 AATTCTGATCCATATTTCA CtMRR1/ Sequencing --- This study

Ct-MRR1-F3 GGGATTAACTTTATATGAAG CtMRR1/ Sequencing --- This study

Cp-MRR1-F4 AATTATACCATGTGTTTG CtMRR1/ Sequencing --- This study

Ct-MRR1-F5 ATGCTAGAAATATGCCAG CtMRR1/ Sequencing --- This study

Ct-MRR1-F6

TGATAAAGAATCTAAAATGAG CtMRR1/ Sequencing --- This study

Ct-MRR1-R1

AACATATCTAATTCACTCA CtMRR1/ Sequencing --- This study

Ct-MRR1-R2 TGTATTGTTCGTGTCTGT CtMRR1/ Sequencing --- This study

Ct-MRR1-R3 CATCAATAAATGGCATGA CtMRR1/ Sequencing --- This study

Ct-MRR1-R4 TCTGGATCTCTGTTTAAC CtMRR1/ Sequencing --- This study

Ct-MRR1-R5 CAATTTGAATGATTTTCTTC CtMRR1/ Sequencing --- This study

Ct-MRR1-R6 CCATAACTTTAGTTTTACC CtMRR1/ Sequencing --- This study

Ct-MRR1-Rexternal

GATATCCCCAATATTTCCG CtMRR1/PCR and sequencing 3639bps This study

Ct-TAC1-Fexternal TTTCTCTAATCATTTGGGG CtTAC1/PCR and sequencing 3099bps This study

Ct-TAC1-F1 GAAGATGAAGAACCTGAA CtTAC1/ Sequencing --- This study

Ct-TAC1-F2 CTTATAGCATTGACTTGC CtTAC1/ Sequencing --- This study

Ct-TAC1-F3 ATTGACTTCGGTATTTC CtTAC1/ Sequencing --- This study

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Table S2. PCR condition and programs used for amplification of target genes.

Loci

PCR Conditions

PCR program

MRR1

Final volume=50µl

10X buffer, 5µl; MgCl2, 2mM, dNTP mix,

0.2mM, Primers Fex and Rex, each 10pm,

Taq polymerase, 2.5 units, MQ water to

adjust in 50 µl

95

º

C, 5min (1 cycle)

35 cycles of; 95

º

C, 30 sec; 52

º

C, 30 sec, and

72

º

C, 4 min

72

º

C, 8 min (1 cycle)

TAC1

Final volume=50µl

10X buffer, 5µl; MgCl2, 2mM, dNTP mix,

0.2mM, Primers Fex and Rex, each 10pm,

Taq polymerase, 2.5 units, MQ water to

adjust in 50 µl

95

º

C, 5min (1 cycle)

35 cycles of; 95

º

C, 30 sec; 52

º

C, 30 sec, and

72

º

C, 3 min

72

º

C, 8 min (1 cycle)

UPC2

Final volume=50µl

10X buffer, 5µl; MgCl2, 2mM, dNTP mix,

0.2mM, Primers Fex and Rex, each 10pm,

Taq polymerase, 2.5 units, MQ water to

adjust in 50 µl

95

º

C, 5min (1 cycle)

35 cycles of; 95

º

C, 30 sec; 52

º

C, 30 sec, and

72

º

C, 2.5 min

72

º

C, 8 min (1 cycle)

ERG11

Final volume=50µl

10X buffer, 5µl; MgCl2, 2mM, dNTP mix,

0.2mM, Primers Fex and Rex, each 10pm,

Taq polymerase, 2.5 units, MQ water to

adjust in 50 µl

95

º

C, 5min (1 cycle)

35 cycles of; 95

º

C, 30 sec; 52

º

C, 30 sec, and

72

º

C, 2 min

72

º

C, 8 min (1 cycle)

HS1 and HS2 of FKS1

Final volume=50µl

10X buffer, 5µl; MgCl2, 2mM, dNTP mix,

0.2mM, Primers Fex and Rex, each 10pm,

Taq polymerase, 1.25 units, MQ water to

adjust in 50 µl

95

º

C, 5min (1 cycle)

35 cycles of; 95

º

C, 30 sec; 52

º

C, 30 sec, and

72

º

C, 30 sec

72

º

C, 8 min (1 cycle)

(4)

No. Age/s

ex City/Hospital/Ward hospitalizaDate of tion Date of discharge/d eath Hospitalizati on duration (Days)

Inpatient Catheter Surgery Parenter

al nutrition

SU-221 57/M Shiraz/Namazi/General 23/05/2017 12/06/2017 20 Yes Central venous No No

SU-231 61/F Shiraz/Namazi/General 05/09/2017 25/09/2017 20 Yes Central venous No No

SU-235 50/M Shiraz/Namazi/Infectious 21/08/2017 30/09/2017 39 Yes Central venous Abdominal No

SU-239 52/M Shiraz/Namazi/ICU 10/08/2017 11/10/2017 61 Yes Central venous No No

SU-267 35/F Shiraz/Namazi/General 28/11/2017 06/01/2018 39 Yes Central venous No No

10 BC 65/F Tehran/Imam/ICU 02/12/2017 07/04/2018 130 Yes Central venous Abdominal No

11BC

36/M Tehran/Imam/Infectious 15/01/2018 13/03/2018 62 Yes Central venous abdominalNon- No 24 BC 38/M Tehran/Imam/Neurology 05/01/2018 22/04/2018 109 Yes Central venous,

Urinary No No

75 BC 32/M Tehran/Imam/ICU 17/04/2018 20/06/2018 62 Yes No No No

82 BC

89/M Tehran/Imam/Pulmonary 22/07/2018 28/07/2018 37 No Urinary abdominalNon- No

85(1)

BC 56/F Tehran/Imam/Surgical 25/07/2018 29/07/2018 5 Yes Central venous,Urinary abdominalNon- No

99 BC 60/F Tehran/Imam/Emergency/ICU 26/07/2018 29/07/2018 3 Yes Central venous Abdominal No

107 BC

53/F Tehran/Imam/Surgical 14/07/2018 03/09/2018 51 Yes Central venous abdominalNon- No 113(1)

BC 54/M Tehran/Imam/ICU 21/08/2018 29/08/2018 8 Yes No No No

113(2)

BC 54/M Tehran/Imam/ICU 21/08/2018 29/08/2018 8 Yes No No No

115(1)

BC 37/F Tehran/Imam/General 19/08/2018 05/09/2018 54 Yes Central venous,Urinary No No

115(2)

BC 37/F Tehran/Imam/General 19/08/2018 05/09/2018 54 Yes Central venous,Urinary No No

E-209

3/M Esfahan/Children's MedicalCenter/PICU 14/01/2015 12/02/2015 28 Yes Central venous,Urinary No Yes E-230 3/F Esfahan/Children's Medical

Center/PICU 22/01/2015 06/03/2015 42 Yes Central venous,Urinary Abdominal No E-240

2/F Esfahan/Children's MedicalCenter/PICU 21/02/2015 26/03/2015 35 Yes Central venous Abdominal Yes E-262

2/F Esfahan/Children's MedicalCenter/PICU 21/02/2015 26/03/2015 35 Yes Central venous No No E-368 4/F Esfahan/Children's Medical

Center/CICU 24/06/2015 12/07/2015 18 Yes Central venous Abdominal No

E-369

4/F Tehran/Children's MedicalCenter/PICU 01/04/2015 30/04/2015 30 Yes Central venous Abdominal No E-511

1/M Esfahan/Children's MedicalCenter/PICU 01/01/2016 13/01/2016 13 Yes Central venous No No E-527 10/M Esfahan/Children's Medical

Center/PICU 25/01/2016 19/02/2016 24 Yes Central venous,Urinary No No

(5)

Center/NICU E-614 1/M Esfahan/Children's Medical

Center/PICU 22/05/2016 18/06/2016 26 Yes Central venous,Urinary No Yes

E-629

14/M Esfahan/Children's MedicalCenter/PICU 10/05/2016 08/06/2016 20 Yes Central venous,Urinary No No E-699 8m/M Esfahan/Children's Medical

Center/CICU 08/09/2016 05/10/2016 27 Yes Central venous Abdominal Yes

E-703 2m/M Esfahan/Children's Medical

Center/CICU 17/09/2016 17/12/2016 61 Yes Central venous Abdominal Yes

E-787 4/F Esfahan/Children's Medical

Center/PICU 03/06/2017 28/06/2017 25 Yes Central venous,Urinary Abdominal No E-1013 40/F Esfahan/Children's Medical

Center/NICU 01/10/2017 29/10/2017 28 Yes Central venous No Yes

E-1014 11/M Esfahan/Children's Medical

Center/PICU 20/04/2018 11/06/2018 52 Yes Central venous,Urinary No No

4M 70/M Mashhad/22Bahman/General 10/02/2018 30/02/2018 20 Yes Central venous No No

8M

28/F Mashhad/22Bahman/General availableNot Not available Not available availableNot Not available Not available availableNot

N15 90/M Mashhad/22Bahman/General 01/03/2018 26/03/2018 26 Yes Urinary No Yes

N17 70/M Mashhad/Arya/General 25/12/2017 02/02/2018 65 Yes Central venous,

Urinary No No

N18 78/M Mashhad/22Bahman/General 10/02/2018 05/03/2018 25 Yes Central venous No No

N26 78/M Mashhad/Arya/General 24/03/2018 29/04/2018 35 Yes Urinary No Yes

N43 85/M Mashhad/22Bahman/ICU 25/04/2018 15/05/2018 20 Yes Central venous No No

N68 1.5/M Mashhad/Sheykh (21)/General 10/09/2016 25/09/2016 15 Yes Central venous No No

N69 1.5/M Mashhad/Sheykh (21)/General 14/03/2018 26/03/2018 12 Yes Central venous No No

N71 8/M Mashhad/Sheykh (23)/ICU 29/01/2017 15/02/2017 16 Yes Central venous

Non-abdominal No

N72 3/F Mashhad/Sheykh

(25)/Emergency 31/08/2017 23/10/2017 53 Yes Central venous No No

N78 3/F Mashhad/Akbar (31)/Surgery 26/03/2016 20/04/2016 26 Yes Central venous Abdominal No

N98 49/F Mashhad/Imam Reza/Burning Not

available Not available Not available availableNot Not available No data availableNot

N104 58/M Mashhad/Imam Reza/General 02/10/2017 08/11/2017 36 Yes No Abdominal Yes

N107 30/F Mashhad/Imam Reza/Burning 12/11/2016 `10/12/2016 28 Yes Urinary Abdominal No

N111 72/M Mashhad/Imam Reza/General 21/11/2016 30/12/2016 40 Yes Urinary

Non-abdominal No

N140 38/F Mashhad/Imam Reza/General 03/11/2016 12/12/2016 39 Yes No No Yes

N147 42/F Mashhad/Imam Reza/General 09/06/2015 16/07/2015 37 Yes No

Non-abdominal Yes

N163 39/M Mashhad/Imam Reza/General 31/08/2015 10/10/2015 41 Yes Urinary

Non-abdominal Yes

N186 63/M Mashhad/Imam Reza/ICU 25/12/2017 02/02/2018 65 Yes Urinary Abdominal Yes

N195 66/F Mashhad/Imam Reza/Infectious 10/02/2018 05/03/2018 25 Yes Urinary No Yes

N198

58/M Mashhad/Imam Reza/ICU 16/11/2016 17/02/2017 103 Yes No data No availableNot

(6)

N210 54/F Mashhad/Imam Reza/ICU 26/10/2015 06/12/2015 40 Yes No Abdominal Yes

N211 56/F Mashhad/Imam Reza/General 25/04/2018 15/05/2018 20 Yes Urinary No Yes

N218 34/F Mashhad/Imam Reza/Burning 26/02/2016 07/03/2016 12 Yes No No Yes

7ALZ 30/M Mashhad/Ghaem/General 20/02/2018 05/04/2018 46 Yes Central venous Abdominal No

8ALZ 29/M Mashhad/Ghaem/Hematology 24/04/2018 11/05/2018 17 Yes Central venous No No

10ALZ 29/M Mashhad/Ghaem/ICU 29/01/2018 05/03/2018 35 Yes Central venous,

Urinary No No

11ALZ 29/M Mashhad/Ghaem/Hematology 20/02/2018 30/03/2018 40 Yes Central venous No No

62ALZ 39/M Mashhad/Ghaem/ Maternity 24/05/2018 01/07/2018 37 Yes Central venous Abdominal No

ICU: Intensive Care Unit, PICU: Pediatric Intensive Care Unit, CICU: Cardiac Intensive Care Unit, NICU: Neonatal Intensive Care Unit, CAS: Caspofungin, FLZ: Fluconazole, NYS: Nystatin, AMB: Amphotericin B, M: Male, F: Female, m: Month.

Supplementary Table S3a. Continue. No. Mechanic

al ventilati

on

Immunosuppres

sant used Neutropenia Underlying conditions exposure with14 days prior antibiotics

Specim en type

Antifungal treatment

(Drug/Dosages/Duration) Outcome Prophilaxy

SU-221 Yes No No Brain tumor, Diabetes Vancomycin,

Ciprofloxacin Blood None Died

SU-231 No Yes No Pneumonia Vancomycin,

Ciprofloxacin, Blood NYS/100,000U/ml/drop/1 day Survived

SU-235 No Yes No GI bleeding, Colon cancer Ceftriaxone,

Clindamycin Blood CAS/50mg/14 days Died

SU-239 Yes Yes No Vascular and heart events Ceftriaxone,

Vancomycin, Cefazolin Blood NYS/100,000U/ml/drop/1 day Died

SU-267 No No No GI bleeding, Addict Vancomycin, Cefazolin Blood None Survive

d FLZ/100mg/10days 10 BC

Yes No No tumors, Abdominal surgeryDialysis, Sepsis, Solid Meropenem,Vancomycin,

Ciprofloxacin Blood

CAS/70mg/stat/50mg/daily/3 days -

L-AMB/3mg/kg/7 days Died 11BC

Yes No No Chronic lung diseases Meropenem,Vancomycin,

Ciprofloxacin Blood FLZ/400mg/daily/14 days

Survive d 24 BC

No No No Cerebral events, Chroniclung diseases, Paraplegia/Auto immune Meropenem, Vancomycin Blood FLZ/400mg/daily/2 days + CAS/70mg/stat/50 mg/daily/2days- L-AMB/3mg/kg/10 days Survive d FLZ/200mg/11days

75 BC Yes No Yes Solid tumors, Abdominal

events Not available Blood FLZ/400mg/daily/14 days Survived

82 BC No No No Cerebral events, Chronic

lung diseases Ciprofloxacin,Clindamycin Blood None Survived

85(1)

BC No No No Dialysis, Solid tumors, Renaldisease Imipenem Blood CAS/70mg/stat/50 mg/daily/5 daysFLZ/400mg/daily/10 days, Died FLZ/400mg/23days 99 BC

(7)

Surgical location infection 107 BC

Yes No No heart events, Hepatitis CDiabetes, Vascular and infection Meropenem, Vancomycin, Cefepime, Metronidazole, Linezolid, Rifampin

Blood CAS/70 mg/7 days Survived

113(1) BC

Yes No No

Diabetes, Dialysis, Vascular and heart events, Chronic lung diseases, Solid tumors,

Renal disease Vancomycin, Meropenem, Piperacillin-Tazobactam, Metronidazole, Cefepime

Blood CAS/50 mg/30 days Died

113(2) BC

Yes No No

Diabetes, Dialysis, Vascular and heart events, Chronic lung diseases, Solid tumors,

Renal disease Vancomycin, Meropenem, Piperacillin-Tazobactam, Metronidazole, Cefepime

Blood CAS/50 mg/30 days Died

115(1) BC

Yes No No Sepsis, Leukemia

Vancomycin, Meropenem, Piperacillin-Tazobactam, Metronidazole, Clindamycin

Blood CAS/70mg/stat/50 mg/daily/3 daysFLZ/400mg/daily/2 days, Died FLZ/400mg/43days

115(2) BC

yes No No Sepsis, Leukemia

Vancomycin, Meropenem, Piperacillin-Tazobactam, Metronidazole, Clindamycin

Blood CAS/70mg/stat/50 mg/daily/3 daysFLZ/400mg/daily/2 days, Died FLZ/400mg/28days

E-209

Yes No No Sepsis Clindamycin,Ceftazidime,

Meropenem Blood AMB/15mg/kg/IV/7 days

Survive d E-230

Yes Yes Yes Sepsis, Leukemia

Ceftazidime, Clindamycin, Amikacin, Piperacillin-Tazobactam, Vancomycin, Ampicillin Sulbactam

Blood FLZ/150mg/daily/2 days-AMB/18mg/kg/7 days Died

E-240

Yes No No Solid tumor

Ceftizoxime, Vancomycin, Amikacin, Linezolid,

Metronidazole, Cephalexin

Blood AMB/12mg/kg/5 days Died

E-262 No No No Not available Ceftizoxime,

Vancomycin, Amikacin, Linezolid,

Metronidazole,

Blood CAS/35mg/stat/25mg/daily/7 days Survive d

(8)

Cephalexin E-368

Yes No No Sepsis, Vascular and heartevents

Cephalexin, Imipenem, Vancomycin, Ceftriaxone, Piperacillin-Tazobactam

Blood FLZ/150mg/daily/2 days +AMB/18mg/daily /10 days Died E-369

Yes No No Sepsis, Vascular and heartevents

Cephalexin, Imipenem, Vancomycin, Ceftriaxone,

Piperacillin-Tazobactam Blood

CAS/56mg/stat/40mg/daily/3 days Survived E-511

No Yes Yes Leukemia, Sepsis

Ceftazidime, Meropenem, Vancomycin,

Piperacillin-Tazobactam Blood

L-AMB/20mg/3 days Died E-527 No No No Sepsis Ceftazidime, Meropenem, Vancomycin, Piperacillin-Tazobactam

Blood AMB/100mg/kg/7 days Died

E-528 Yes No No Sepsis Meropenem, Vancomycin, Colistin, Ampicillin, Cefotaxime,

Blood AMB/2.5mg/kg/10 days Survived E-614

Yes No No Sepsis, Dialysis

Amikacin, Gentamycin, Linezolid,

Metronidazole, Vancomycin

Blood AMB/12mg/kg/7 days Died

E-629

Yes Yes yes Leukemia, Dialysis, Sepsis

Cefixime, Meropenem, Vancomycin, Trimethoprim-Sulfamethoxazole, Amikacin, Ampicillin Sulbactam Blood

AMB/50mg/kg/10 days Died

E-699

Yes Yes No Sepsis, Vascular and heartevents Ceftazidime,Vancomycin,

Amikacin, Gentamycin Blood AMB/10mg/kg/10 days

Survive d E-703

Yes No No Vascular and heart events

Vancomycin, Trimethoprim-Sulfamethoxazole, Ceftazidime, Piperacillin-Tazobactam, Cefepime.

Blood FLZ/25mg/daily/2 days survived

E-787 No No Yes Solid tumors Ceftriaxone,

Ceftizoxime, Vancomycin,

Blood FLZ/150mg/daily/14

(9)

Imipenem E-1013 No No No Sepsis Ceftazidime, Vancomycin, Piperacillin-Tazobactam, Clindamycin, Amikacin

Blood AMB/3mg/kg/10 days Survived E-1014

Yes Yes Yes Sepsis

Amikacin, Gentamycin, Linezolid,

Metronidazole, Vancomycin

Blood CAS/60mg/stat/45mg/daily/3 days-AMB/30mg/kg/10 days Died

4M Yes No No Diabetes, Chronic lung

diseases Meropenem,Ceftriaxone Tracheal FLZ/400mg/daily/10 days -AMB/3mg/kg/7 days Survived

8M Not

available Not available availableNot Not available Amikacin, Ceftazidime,Clindamycin Blood None Died

N15 Yes No No Diabetes, Chronic lung

diseases Vancomycin,Meropenem Blood FLZ/200mg/kg/daily/2 days Survived

N17 No No No Diabetes, Chronic lung

diseases Vancomycin,Meropenem Tracheal FLZ/400mg/daily/7 days +AMB/3mg/kg/7 days Died

N18 Yes No No Chronic lung diseases Vancomycin,

Meropenem Tracheal FLZ/150mg/daily/10 days,AMB/3mg/kg/10 days Died N26

Yes No No Sepsis, Chronic lungdiseases Ciprofloxacin,Vancomycin,

Ampicillin Blood AMB/50mg/kg/7 days

Survive d N43

Yes No No heart events, Chronic lungDiabetes, Vascular and diseases

Ciprofloxacin,

Meropenem Tracheal AMB/3mg/kg/2 days Died

N68 No Yes Yes Leukemia, Sepsis Amikacin, Ceftazidime,

Clindamycin Blood AMB/50mg/kg/19 days Died

N69

No Yes Yes Leukemia, Sepsis Amikacin, Ceftazidime,Clindamycin Blood AMB/50mg/kg/10 days Survived N71 Yes Yes No Leukemia, Sepsis, Bone pain Amikacin, Ceftazidime,

Vancomycin Blood AMB/50mg/kg/2 days Survived

N72 No No No Disease syndrome, Fever,

Respiratory distress Amikacin, Ampicillin,Vancomycin Blood None Died

N78 No No No Sepsis, Biliary obstruction,

Heart failure (Heart arrest) Metronidazole Blood None Died

N98 Not

available Not available availableNot Not available Not available Blood Not available Survived

N104 Yes No No Stomach bleeding Azithromycin,

Ceftriaxone Blood AMB/50mg/kg/10 days Died

N107 Yes No No Diabetes, Sepsis, Abdominal

events Colistin, Ciprofloxacin Blood FLZ/200mg/daily/2 days Survived

N111 Yes No No Sepsis Ciprofloxacin Blood AMB/50mg/kg/12 days Died

N140

Yes No No Sepsis Vancomycin,Ceftazidime,

Ciprofloxacin Blood None Died

(10)

Imipenem, Colistin

N163 Yes No No Sepsis, Burning Vancomycin,

Ceftriaxone Blood AMB/50mg/kg/10 days Died

N186

Yes No No Diabetes, Dialysis, Sepsis Vancomycin,Meropenem,

Methicillin Blood None

Survive d N195

Yes No No Sepsis Vancomycin,Meropenem,

Ciprofloxacin Blood FLZ/200mg/daily/4 days

Survive d

N198 Not

available Not available availableNot Not available Vancomycin, ColistinMeropenem, Blood FLZ, CAS, AMB Died N208

Yes No No Sepsis Ciprofloxacin,Meropenem,

Vancomycin. Blood NYS/100,000U/ml/drop/1 day Died N210

Yes No No Sepsis, Burning

Ceftazidime, Imipenem, Gentamycin, Vancomycin, Ciprofloxacin, Amikacin

Blood None Died

N211 Yes No No Sepsis Vancomycin,

Ceftazidime Blood None Died

N218

Yes No No Sepsis Metronidazole,Penicillin,

Cefalotin, Cephalexin Blood None Died

7ALZ No No No Sepsis, Bedridden Ceftriaxone, Ciprofloxacin, Clindamycin, Vancomycin

Blood AMB/50mg/kg/6 days Died

8ALZ

No Yes Yes Leukemia, Sepsis, Mentallyretarded, Emboli Ciprofloxacin,Vancomycin,

Clindamycin Blood None Died

10ALZ

No No No (CABG), Rinse and aspirateDialysis, Heart disease the stomach

Vancomycin, Ciprofloxacin,

Clindamycin, Gentamicin

Blood NYS/100,000U/ml/drop/1 day Died 11ALZ No No No Leukemia, Sepsis Ciprofloxacin, Vancomycin, Meropenem, Gentamicin, Ceftriaxone, Clindamycin

Blood None Died

62ALZ

No No No Cesare, Emboli Cefixime, Meropenem,Vancomycin,

Ceftazidime Blood None

Survive d

ICU: Intensive Care Unit, PICU: Pediatric Intensive Care Unit, CICU: Cardiac Intensive Care Unit, NICU: Neonatal Intensive Care Unit, CAS: Caspofungin, FLZ: Fluconazole, NYS: Nystatin, AMB: Amphotericin B, M: Male, F: Female, m: Month

(11)

Table S3b. Summary of clinical profile of patients suffering from candidemia due to Candida tropicalis.

Variable

N

%

Total number of:

*All calculations are based on

episodes

(isolates with ≥30 days

considered as a new case)

isolates

64

patients

62

episodes (after deletion of

repetitive isolates)

62

Sex

Female

26

41.93

Male

36

58.07

Age

Median

37.1yr

City

Tehran

26

41.93

Shiraz

5

8.06

Mashhad

31

50

Hospital ward

ICU

27

43.54

General

16

25.8

Surgery

3

4.83

Other

16

25.8

In/out patient

Inpatient

61

98.3

Outpatient

1

1.61

Risk factors

Catheter

Yes

53

85.48

No

9

14.51

Surgery

Abdominal surgery

17

27.41

Non-abdominal surgery

8

12.9

Without surgery

37

59.67

(12)

No

42

67.74

Mechanical ventilation

Yes

37

59.67

No

25

40.32

Immunosuppressive drugs

Yes

14

22.58

No

48

77.41

Neutropenia

Yes

12

19.35

No

50

80.64

Underlying conditions

Leukemia

Yes

9

14.51

No

53

85.48

Hematological malignancies

other than leukemia

Yes

0

0

No

62

100

Diabetes

Yes

10

16.12

No

52

83.87

Dialysis

Yes

7

11.29

No

55

88.7

Sepsis

Yes

31

50

No

31

50

Cerebral events

Yes

4

6.45

No

58

93.54

Burning

Yes

3

4.83

No

59

95.16

Vascular and heart events

Yes

8

12.9

No

54

87.09

Chronic lung diseases

Yes

12

19.35

No

50

80.64

Solid tumor

Yes

7

11.29

No

55

88.7

Trauma and fracture

Yes

0

0

No

64

100

Abdominal events

Yes

10

16.12

No

52

83.87

(13)

No

61

98.38

Other

Yes

12

19.35

No

50

80.64

Hospitalization duration

Median

≤30

30

48.38

30-90

29

46.77

>90

3

4.83

Crud mortality rate for C.

tropicalis

Died

Survived

37

25

59.67

40.32

Mortality rate for C. tropicalis per

city

Tehran

Shiraz

13

3

60

50

Mashhad

21

67.74

Mortality per treatment

No treatment

12

30.77

Monotherapy

15

43.59

Combination therapy

10

25.64

Treatment

FLZ (11 in combination)

16

25.8

AMB (10 in combination)

28

45.16

CAS (5 in combination)

11

17.74

VOR

0

0

NYS

4

6.45

Mortality per treatment

FLZ

8

50

AMB

18

64.28

CAS

9

81.81

VOR

0

0

(14)

Table S4. Antifungal susceptibility testing data and sequencing of genes conferring resistance to fluconazole.

Patient # Genotype FLZ VRZ MIC values (µg/ml)ITZ MFG AFG AMB ERG11 MRR1 TAC1 UPC2

N4 G4 1 0.5 0.25 1 0.5 1 WT ND ND ND

N8

G5 0.5 0.125 0.5 0.062 0.062 0.5

WT G259R (A87T), T398C (V133A), G3066A (M1022I), C3125A (T1042N), C3131A (T1044N),

A3390G (I1130M) WT G751R (A251T), A866W (Q289L), G1175R (G392E) N15 G2 0.5 0.125 0.125 0.016 0.016 0.25 WT WT T833C (L278S) A293R (N98S), T472K (L158V) N17 G4 4 0.5 1 0.125 0.062 1

WT C1568Y (S523F), A2269R (K757E), A3390R (I1130M) T833C (L278S), T1019W (L340*), G1049R (D350N), T1410G (F470C), G2369A (D790N) NA N18 G4 2 0.62 0.5 0.125 0.031 0.5 WT ND ND ND N26 G6 2 0.5 0.125 0.125 0.062 1 WT C1568T (S523F), A2269R (K757E) T833C (L278S), G1048R (D350N),

T1409G (F470C), G2367A (D790N) G889K (A297S), G1175R(G392E)

N43 G1 2 0.125 0.5 0.031 0.031 0.5 WT ND ND ND N68 G6 0.5 0.5 0.25 0.5 0.5 0.5 WT ND ND ND N69 G6 2 1 0.25 0.031 0.016 1 WT ND ND ND N71 G9 0.125 0.016 0.125 0.008 0.008 1 WT C1568T (S523F), A2269R (K757E) T833C (L278S), G1048R (D350N), T1409G (F470C), G2367A (D790N) G1175R (G392E) N72 G3 0.5 0.25 0.125 0.16 0.008 0.25 WT ND ND ND N78 G4 1 0.031 0.5 0.031 0.008 0.5 WT ND ND ND N98 G4 1 0.5 0.25 0.008 0.008 0.5 WT ND ND ND N104 G4 1 0.25 0.25 0.062 0.031 1 WT G3066R (M1022I), C3125M (T1042N), C3131M (T1044N), T3286W (D1092E), A3390R (I1130M)

T833C (L278S) WT N107 G4 1 0.062 0.25 0.062 0.062 1 WT ND ND ND N111 G4 0.25 0.016 0.25 0.062 0.031 0.5 WT ND ND ND N140 G4 1 0.5 0.25 0.008 0.008 0.5 WT ND ND ND N147 G4 0.5 0.031 0.125 0.062 0.062 0.5 WT G3066R (M1022I), C3125M (T1042N), T833C (L278S), C3131M (T1044N), T3286W (D1092E), T833C (L267S) WT

(15)

A3390R (I1130M) N163 G3 1 0.062 0.125 0.016 0.016 0.5 A269W (K90I) ND ND ND N186 G4 2 1 0.25 0.008 0.008 1 WT ND ND ND N195 G4 0.25 0.031 0.125 0.008 0.008 0.5 WT C1568T (S523F), A2269R (K757E) T833C (L278S), G1048R (D350N), T1409G (F470C), G2367A (D790N) G889K (A297S), G1175R (G392E) N198 G1 0.25 0.031 0.5 0.125 0.125 1 WT ND ND ND N208 G4 0.5 0.25 0.25 0.062 0.008 0.5 WT ND ND ND N210 G2 0.125 0.062 0.125 0.125 0.125 0.25 WT WT T833C (L278S) A293R (N98S), T472K (L158V), G751R (A251T) N211 G4 1 0.062 0.25 0.062 0.008 0.5 WT ND ND ND N218 G4 0.25 0.016 0.5 0.5 0.25 1 WT ND ND ND SU-221 G5 0.03 0.015 0.06 0.25 0.125 1

WT G259R (A87T), T398Y (V133A), G3066A (M1022I), C3125A (T1042N), C3131A (T1044N),

T3286W (D1092E), A3390G (I1130M)

T833C (L278S), T1409G (F470C) WT SU-231 G4 0.125 0.06 0.125 0.25 0.125 1 WT ND ND ND SU-235 G2 0.125 0.125 0.125 0.062 0.031 1 WT WT T833C (L278S) A293R (N98S), T472K (L158V), G751R (A251T) SU-239 G2 4 0.06 0.125 0.25 0.25 1 WT WT T833C (L278S) T472Y (L158V), A293R (N98S), T472K (L158V), T1712W (F571Y) SU-267

G1 0.125 0.125 0.125 0.062 0.062 1 A73G (I25A)and T74C (I25A)

WT T833C (L278S), T1409G (F470C),

A2650G (S884G) A293R (N98S), C355M (L119F),G439R (A147T), T472K (L158V) 7ALZ G5 0.25 0.031 0.5 0.125 0.125 1 WT ND ND ND 8ALZ G5 0.5 0.062 0.5 0.062 0.062 0.5 WT ND ND ND 10ALZ G4 0.25 0.25 0.125 0.016 0.016 1 WT ND ND ND 11ALZ G4 1 0.125 0.125 0.125 0.062 0.5 WT ND ND ND 62ALZ G4 0.25 0.016 0.5 0.5 0.25 1 WT ND ND ND

10BC G6 1 0.5 0.5 0.007 0.062 0.5 WT T1223Y (I408T), G3066R (M1022I), C3125M(T1042N), C3131M (T1044N), T3286W (D1092E), A3390R (I1130M)

T833Y (L278S), T1409G (F470C),

G2367R (D790N), G2368R (D790N) (Q289L), G889K (A297S)G751R (A251T), A866W

11BC G2 1 0.5 0.5 0.062 0.062 0.5 WT ND ND ND

(16)

75BC G4 4 0.125 0.25 0.031 0.012 1 WT C1568Y (S523F), A2269R (K757E), A3390R(I1130M) T833Y (L278S) WT

82BC G4 4 1 0.25 0.062 0.062 0.5 WT A3390G (I1130M) WT G877A (A263T)

85BC G2 2 0.25 0.125 0.031 0.125 1 WT WT T833C (L278S) A293R (N98S), T472K (L158V)

99BC G5 8 1 0.5 0.031 0.125 2

WT T398Y (V133A), G1939K (A647S), G3066R (M1022I), C3131M (T1044N), T3286W (D1092E),

A3390G (I1130M)

T833C (L278S), T1409G (F470C)

WT 107BC G3 4 0.062 0.125 0.062 0.062 0.5 WT C1568T (S523F), A2269G (K757E) T833C (L278S), T1409G (F470C),G2367A (D790N) WT

113-1BC G4 4 1 0.125 0.007 0.06 1 WT A3390G (I1130M) T833C (L278S), T1409G (F470C) G751R (A251T), A866W(Q289L)

113-2BC G2 8 0.062 0.25 0.125 0.062 0.125

WT WT T833C (L278S) A293R (N98S), T472K (L158V),

A689R (N230S), A721R (T241A)

115-2BC G5 4 0.5 0.06 0.015 0.015 1

WT G259A (A87T), T398C (V133A), G3066A (M1022I), C3125A (T1042N), C3131A (T1044N),

A3390G (I1130M)

WT G751R (A251T), A866W

(Q289L), G1175R (G392E) 115-1BC G5 0.5 0.125 0.125 0.016 0.031 0.5 WT (M1022I), C3125A (T1042N), C3131A (T1044N),G259A (A87T), T398C (V133A), G3066A

A3390G (I1130M) WT G751R (A251T), A866W (Q289L), 209E G6 1 0.5 0.125 0.016 0.016 0.5 WT ND ND ND 230E G6 1 0.062 0.25 0.062 0.062 0.25 WT ND ND ND 240E G4 0.25 0.031 0.125 0.016 0.016 0.5 WT ND ND ND

262E G4 64 4 16 0.008 0.008 1 WT (T1044N), T3276W (D1092E), A3390R (I1130M)G3066R (M1022I), C3125M (T1042N), C3133M G140A (R47Q), A491T (N164I), T833C(L278S) T1020A (Q340H), T1141A(T381S)

368E G6 0.5 0.25 0.25 0.031 0.008 0.5 WT ND ND ND

369E G10 0.25 0.062 0.25 1 0.5 0.5 WT ND ND ND

511E G6 0.25 0.062 0.25 0.062 0.062 1 WT ND ND ND

527E G8 8 1 0.5 0.031 0.016 1

WT A763M (T255P) G140A (R47Q), A491W (N164I),

T833C (L278S), T1409G (F470C), G2367R and G2368R (D790N) G439R (A147T), G751W(A251T), A866W (Q289L) 528E G6 0.5 0.062 0.25 0.125 0.008 0.5 WT ND ND ND 614E G2 0.5 0.25 0.125 0.016 0.031 0.5 WT ND ND ND 629E G5 0.5 0.125 0.25 0.125 0.016 1 WT ND ND ND 699E G2 0.5 0.25 0.25 0.031 0.031 0.5 WT ND ND ND

(17)

703E G6 0.5 0.062 0.25 0.008 0.062 1 WT ND ND ND

787E G7 0.5 0.031 0.25 0.031 0.125 1 WT ND ND ND

1013E G5 0.5 0.062 0.125 0.031 0.031 0.25 WT ND ND ND

1014E G4 1 0.25 0.5 0.062 0.008 0.5 WT ND ND ND

*; Stop codon,

ND; Not determined, NA; Not amplified WT; Wild-type, G; Genotype, FLZ; Fluconazole, VRZ; Voriconazole, ITZ; Itraconazole, MFG; Micafungin, AFG; Anidulafungin,

and AMB; Amphotericin B. Regardless of MIC values, all the sequences of HS1 and HS2 of FKS1were wildtype. HS1 and HS2 of FKS1 amino acid sequences are

(18)

Statistical analysis section

Genotype and hospitalization duration association

G2

G3

G4

G5

G6

27

53

20

20

61

26

51

65

46

18

5

41

25

17

130

40

26

3

109

39

15

54

28

62

36

54

42

61

28

20

13

8

40

28

30

26

39

20

35

37

15

25

12

20

12

20

35

40

37

62

37

8

35

35

52

65

(19)

As the hospitalization duration data were not normally distributed, first they were normalized using Kolmogorov Smirnov.

Tests of Normality

Kolmogorov-Smirnova Shapiro-Wilk

Statistic df Sig. Statistic df Sig.

HosDuration .145 56 .005 .864 56 .000

a. Lilliefors Significance Correction

In order to assess the association between genotypes and hospitalization duration we used the non-parametric Kruskal Wallis Test and the association was not

significant.

Test Statistics

a,b

HosDuration

Chi-Square 2.754

df 4

Asymp. Sig. .600

a. Kruskal Wallis Test b. Grouping Variable: Genotype

Association between genotype and fluconazole susceptibility profile using Chi-Square and lack of significant association between these two variables.

Genotype

G2

G3

G4

G5

G6

FLZ-R

1

0

1

1

0

FLZ-S

7

1

19

7

11

(20)

Genotype * FLZ Crosstabulation

Count FLZ Total R S SDD Genotype G2 1 7 1 9 G3 0 1 2 3 G4 1 19 4 24 G5 1 7 1 9 G6 0 11 0 11 Total 3 45 8 56

Chi-Square Tests

Value df Asymptotic Significance (2-sided) Pearson Chi-Square 10.854a 8 .210 Likelihood Ratio 10.376 8 .240 Linear-by-Linear Association .483 1 .487 N of Valid Cases 56

(21)

a. 11 cells (73.3%) have expected count less than 5. The minimum expected count is .16.

Association between genotype and voriconazole susceptibility profile using Chi-Square and lack of significant association between these two variables.

Genotyp

e

G2

G3

G4

G5

G6

VRZ-R

0

0

4

1

1

VRZ-S

5

2

12

7

4

VRZ-I

4

1

8

1

6

Genotype * VRZ Crosstabulation

Count VRZ Total R S SDD Genotype G2 0 5 4 9 G3 0 2 1 3 G4 4 12 8 24 G5 1 7 1 9 G6 1 4 6 11 Total 6 30 20 56

Chi-Square Tests

(22)

Value df Asymptotic Significance (2-sided) Pearson Chi-Square 6.712a 8 .568 Likelihood Ratio 8.236 8 .411 Linear-by-Linear Association .061 1 .805 N of Valid Cases 56

a. 12 cells (80.0%) have expected count less than 5. The minimum expected count is .32.

Association between genotypes and mortality through multivariate logistic variation and path analysis revealed lack of association between these

variables.

G2

G3

G4

G5

G6

Alive

3

1

10

1

6

Dead

5

2

15

7

5

Genotype * outcome Crosstabulation

Count outcome Total Alive Dead Genotype G2 3 5 8 G3 1 2 3 G4 10 15 25

(23)

G5 1 7 8 G6 6 5 11 Total 21 34 55

Chi-Square Tests

Value df Asymptotic Significance (2-sided) Pearson Chi-Square 3.550a 4 .470 Likelihood Ratio 3.903 4 .419 Linear-by-Linear Association .159 1 .690 N of Valid Cases 55

a. 7 cells (70.0%) have expected count less than 5. The minimum expected count is 1.15.

Variables Alive

B S.E. Wald df Sig. Exp(B)

Step 1a G2 -.693 .949 .534 1 .465 .500

G3 -.875 1.366 .411 1 .522 .417

G4 -.588 .730 .648 1 .421 .556

(24)

Constant .182 .606 .091 1 .763 1.200 a. Variable(s) entered on step 1: G2, G3, G4, G5.

Variables Dead

Score df Sig. Step 0 Variables G2 .002 1 .966 G3 .032 1 .859 G4 .064 1 .800 G5 2.616 1 .106 G6 1.560 1 .212

a. Residual Chi-Squares are not computed because of redundancies.

Wild-type sequences used in this study

ERG11, wild-type

>ERG11 Candida tropicalis MYA-3404 cytochrome P450 51 (CTRG_05283) partial mRNA

ATGGCTATTGTTGATACTGCCATTGATGGCATCAATTATTTCTTATCCTTATCATTAACTCAACAAATCACCATCTTGGTTGTTTTCCCATTCAT

CTACAACATAGCATGGCAATTACTTTACTCCTTAAGAAAAGATAGAGTTCCAATGGTTTTCTACTGGATCCCATGGTTTGGTTCTGCTGCTAGT

TATGGTATGCAACCATACGAATTCTTTGAAAAGTGCAGATTGAAATATGGTGATGTTTTTTCATTTATGTTATTAGGTAAAGTTATGACTGTTT

ATTTGGGTCCAAAAGGTCACGAATTCATTTACAATGCTAAATTATCCGATGTTTCTGCTGAAGAAGCTTATACCCATTTGACTACTCCTGTTTTT

GGTAAAGGTGTTATTTATGATTGTCCAAACTCTAGATTAATGGAACAAAAGAAGTTTGCTAAATTTGCTTTGACTACTGATTCTTTCAAAACCT

ATGTTCCAAAGATCAGAGAAGAAGTTTTGAATTATTTTGTTAACGATGTTAGTTTCAAAACCAAGGAAAGAGACCATGGTGTTGCTAGTGTTA

TGAAAACTCAACCAGAAATCACTATTTTCACTGCTTCTCGTTGTTTATTTGGTGATGAAATGAGAAAGAGTTTCGACAGATCATTTGCTCAATT

GTATGCTGACTTGGATAAAGGTTTCACCCCAATCAACTTTGTTTTCCCAAACTTGCCATTACCTCATTACTGGAGACGTGACGCTGCTCAAAGA

AAGATATCTGCTCATTACATGAAGGAAATTAAGAGAAGAAGAGAAAGCGGTGATATTGATCCAAAGAGAGATTTGATTGATTCCTTGTTGGTT

(25)

AACTCTACTTATAAAGATGGTGTTAAAATGACTGATCAAGAAATTGCTAACCTTTTAATTGGTGTTTTGATGGGTGGTCAACATACTTCTGCTT

CCACTTCTGCCTGGTTCTTGTTGCATTTGGCTGAACAACCACAATTACAAGATGATCTTTACGAAGAATTGACCAACTTGTTGAAAGAAAAGG

GTGGTGACTTGAACGATTTGACTTACGAAGACTTGCAAAAATTACCATTGGTTAACAACACTATTAAAGAAACTTTGAGAATGCACATGCCAT

TGCATTCTATTTTCAGAAAAGTTATGAACCCATTGAGAGTCCCAAATACCAAATATGTTATTCCAAAAGGTCACTATGTCTTAGTTTCTGCCGG

TTATGCTCATACCAGTGATAGATGGTTTGAACACCCAGAACATTTCAACCCAAGAAGATGGGAATCTGATGATACCAAGGCTAGTGCTGTTTC

TTTCAATTCTGAAGATACTGTTGATTATGGTTTCGGTAAAATTTCCAAAGGTGTCTCCTCTCCATACTTGCCATTCGGTGGTGGTAGACACAGA

TGTATTGGTGAACAATTTGCTTATGTTCAATTGGGAACTATTTTGACCACTTATATCTACAACTTCAAATGGAGATTAAACGGTGATAAGGTTC

CAGATGTTGATTACCAATCCATGGTTACCTTACCATTAGAACCTGCTGAAATCGTTTGGGAAAAGAGAGATACTTGTATGGTTTAG

MRR1, wild-type

>CTRG_02269 MRR1 ORF_ONLY CGDID:CTRG_02269 COORDS:Supercontig_3.3_C_tropicalis_MYA-3404:387555-391007C (3453 nucleotides)

Ortholog(s) have RNA polymerase II core promoter proximal region sequence-specr

ATGTCATTTTTACCACCCAAAATACCAGCTAGTTTCATCCATGAATCAATGCAAAATCATGGAGGTGCTAACCAACAAGGAAATAATACCAAT

AATGGTCAATCAGGAGATCAAACAAAGAAAAGAAAAAGAATAAGTTCAGTTTGTACTAACTGTAGAAGACGTAAGATAAAATGTAATAGGG

AATATCCATGTTCAAATTGTGTTAAAGCTAAACGTCAAACAAGTTGTGTTTATGATGATGGGATTATTCATACTGCTACTACTACTAATGCTAG

TAGTACAAATGAGAATAAGAATAAAATGTCTTCAATACCTGAGAATAGTTCAAATTATTATTTGTCTAGTGTTAGAACTCCAATTAAGTTTGAT

AAGGATGTGACTTCAAATTCATCAGTGAACTATGATAATAATTCAAGAAAGAAATCAAAAACTAGTTCTATTTCAAGTCTGATTAGTAATGGT

TCAAATATTAATGGAGATGATCAAAATAATATAACAATGAGTGAATTAGATATGTTGAAACAAAGATTAGAAAGTATTGAATCTAGAATTAA

TGGTGAAACAACTCCTATTCCATTAGTAGCTCCTCCATCAACAACAAATAATTCCAATAATGGTAATAATATTTTACCACCACCTGTTAAATTC

AATAGTTTAAGTCCACAAAATAAACCTGAATCACTTATGTTCACACCACCTTGTCCAACTCCTCCTAGTACCATACCTCATCGTCCACCACCTT

CAATGAATAGATTTCAAACAACTTATAATGTATCACATACTAGAGGGACCCCATCTCCTGGTATTCAATTACCCCCAATTAATGTAAGAGAAC

AAGATAACAGAAATAATAACAATATGATTCCAACAAATGTTTCATATAGTTCAGTATCCAATAATTCTGATCCATATTTCAAAACTCCGGATT

CATCAGTTTCCAATAAGTCTCCTCATAATAGTATTAGTTCTGTTCGCACAGACACGAACAATACATTAATTGGAGTTAATCCATATTTGGATGA

AAATGAAACAATTAATTTTTATGAAGGATATACTTCAATTTGTATTAAAGATTATCGAAGAATCAATCATGGTCCATTTGCCTGGAGTTCCTTA

ATGAAAAAGGATAAAGCGTTGAGTTTGTTATGGTTACATATTTGTAAATTGAAAGAGGAAAAGAGTCAACAAAATTTCATATTTGGACTGTCT

GTTAGTGAAATTAATCAAGAAAATACGTCATTAGTAACATCCGAATCAAATGAAAGTGAAGTTAATTTTAAAAAGAAGACTTTAGAAAGTTTT

GGATATAAAGATATTGTTCCATATGATGTGTTGAAGAAAAAACTCAAGAAAGAATTAAATCAAGTTTCATTACCCTTGGGATTAACTTTATAT

GAAGAACAAGTTAATGCTGAATTACAATTAGTTGATAGAATTCATCAGTTATTACCTAAACAAAAAGTTATTTGGAAATCTTTGGATAGATTT

TTCTCTTTACTTTATCCATTCATGCCATTTATTGATGAATATGATTTCACTGATTCAATAAGTAAAATAATTGGATCCAAAAATTATAAAGATG

AAAAGATTAAAGAAATTAAAGTTGAAAAACGATTAGATTTGGCATATTTGGGATTATTATTGATTGTTTTAAGATTAAGTTATTTATCATTATT

TTCAAATAAAGAAAGTGTTAATGAAATGAGACTCAATTCAACTGATCCTTCAGAAGAAGCACAAGATTTGAAGTATTTAATTCAAAATCCAAT

TGGTATTTCATTTATTGATACTGCTCATTTATGTTTAAATCAATTTGATATTTTCCGAAAAGCTGCAATGTCAGTATTGCAACTTGCATTTTATT

(26)

TACAATTATACCATGTGTTTGCACCTGAGGATGGAGATGACGGAGATGGAGCAGATACTTATGCTTTAAATGCAATGATTGTACAAATGGCGT

ATTCACTTGGGTTAAACAGAGATCCAGATAATTTCCCCGATGTCTTAAATAATAAACGAGAAAATAATATGGGAAGAAAGATTTGGCATTTTA

TGATTTTAACAGATATTCATCATTCTTATAGTTTTGGTAATCCAAGAACTATATGTGATCAATATTTTGATACAAAATTACCCTTTGTTGAAGA

AGGAGCTGAAAATTTACGTGACAAGAAATTGGATAATTTTGTCACTCTGAATTTCCCTGGCTATTTGCCAGTTTATGATATTTTAAGTGATATT

TTGAAATTAATTCTTAATGTATCAGGGAAAGTTAAAATGTCACAATTATGTAAATTATTAAGTGAATTTGAAACCAGTATTTATGAAAAATAT

GGTACTTTATCAGATTGTTTGAATCCAAAGAATTGTTCATTTAATCATATTTATGCTAGAAATATGCCAGTTAAATTATATATTTCTTTAAAATC

ATTTTTGGTTTCTGTTTATTTCCATATTTTCTTGTATTATGAAAAGAAAGATTTGAAATTGTCATATTTTTATTTGAAGAAAATCATTCAAATTG

CTGCTACTGATATCATGCCTCATTATTTTGAATTATTAGGTAATAGTGAAGTTGTATGTGATATGGTTATAAATCCAAAATTGATTCAAATTAT

TCATAAATTAATCCAGGTTAATTTAGCATTAATATTGAGAGTTAATTTTTCAATTTATTATTTTAAAAATCAAGAAGATCATGGATTTAAATGT

TCTAATGATGAAAAATATTATTCATATTATAAAGAATTATGTAAATTTTCATCAGGTTTAACAAGATGTGCGGAAGTTGGGGTAGCAGCGGTT

TCAAAATTAAGTACAAGATATTATTATGCATGGAAAGTAACCAAAGCAAATAATTATTTATTGAAAAAGATAACAACTATGGAATTTTATGAT

AAAGAATCTAAAATGAGTAATAAATTAATGTTACCAAATTATTCAATTGAAGAAATTCAAGAATTAGGATTAATGTCAGAAATTGCATTATCA

AAATTAGGTAAAACTAAAGTTATGGGTGATGAATTTTGTACTACTTGTACTTATAAAAATTTCAAATCTGATATGTCTACGACATCATCTGAAA

CAAATCAAACTCCAAATACTGCCACCACCATGAATAGCACCACCACCAACAATAATAATAATAACATCAGTAGTACTAATTCAAATTCTATGA

CAAGTATTTCTGATACGAGAAAATACACTAATGAATTTGGGCTAGATTTTGTTAATAATGAAGATATTGATAAGATTTGGTTACAAATGATTA

CCGATCAACAACAAAAACAAAAACAAAATGAACCTAATACACCTAATTTTTCAATGATGAATTCTCCATATGGTAATATTGCTACCCCAGGTA

ACAATGGTGGATTTAATAATGACATATTTGATCCTAATTCATTTGATATTTTAGTCGATATTGATCGTTTATTAAACAATGATGGATAA

TAC1, wild-type

>PQTP01000012.1:561163-563994 Candida tropicalis MYA-3404 tig00000049_pilon, whole genome shotgun sequence

ATGTCATTTGAAGAAACTACTATGGGTGATTCTTGTAGTGAGTCATATTCTGAAAATTATTCCAATCAAATCGAATTAACAGGAAATGATCCA

AATGATACAACGAGAAAAAGAATTCGAGTTGCTTGTGATACATGTCGAAGGAAAAAGATAAAATGTAACGGGACATTTCCTTGTGCAAATTG

TGTTCAAACTAAAAATGAATCAAGTTGTCATTATACTGAACGTCCTATGAAGAAATCAAAAATTGTCAAAGATAAGAAGGAAACTCTGATATC

TAACAAAAAAGATGATGTAATATCTGTTACAAGTAGTAATGGCGACAATAATGAATTAAAACCAAAAGATAAACCCACAACAAAGTCTAAAT

CCAAATCTAAGAGTCATTCAACTGGTGATATTGAATCTAGACTAAGCTCAATAGAAAATTCTATTCTGAGAATGATGTCAGTTATGGAGAAAC

TTCTGGGGAAGCTAACTTCTCAAAGTAATGGAGAACAAAATATTACGGAAGATGAAGAACCTGAAATTCGAGATCACACAACAACACCATCA

GATTTACAAAATCCCAAGAAAGATTTTAATGATTTAGTAAATTTAAGAAATTGGGACGAGTTTGTGGGTACTCATTCAATAGCTTGTATTTTCT

CAAGGGATTCTTTAGCATGGATGGAACGTGCTTTAGGAGAATATGGAGTGGAATATCTAACACCCATAAGAAACTTACCACTTGTATTTTTCT

CGGAGATGAAACCGTATATTTTAAAATGGGTGGATCCTCCTGTTGTTGATAGACACCAAAAAAGAAGGTTGATGGAGACTCCATTCCCTTTGG

ATGAGAAGTTGGTCATGGGATTGGTTAATTTGTATTATGAAGAAACATCAATTGTGAATACAATTGTAGAGGAGTCTTGGATGAGAGAATTGT

(27)

TTACTAGTTATTTTAAGAATTTAAAAGAAACGGATGCCCGAAAAAGGCGAAGATACAGGTTACCAGAATTATTATCTATGACTTGTGTTTTAC

TTATAGCATTGACTTGCAATACAGAAGATGGTTTGTTTAATTATGATCCTAAAAAATTCCCCAATGAGTATTCTCCAGCTGGTGCATTATTAGA

TGGTTATAGCAGAAAAATGTTGACAGAGTTGCAGGAAAAATTATTTGATAATGCAATTTATTATTACCAACGTGTATCAGTAGTTAGTGAAGG

TATTGAAACAATTGAAGCCTTGTTGTTGTTGATTATTTGCATAGAGTCTAATTGGTTGACAAGTTTTCTTAATAGTTCTCCAATAGCGGTTGCCA

TTCGATTTGCACAAGACCTTGGATTACATCGTGCAGAATCCTATTTAAATAAACCATTGAAGGAACAAGAAAGGAGAAGAAGAGTATGGTGG

TTCTGTTATTTCTTTGATATTGAGTTTTGTTTCAAGTCAGGTAAACCGCCAATGATTAACTCAAGTGATGTTACTACGAATAGTGATGAAGATT

TGTTGCAGTATTTCAAACTAACTGCTGCTGAAGCACCACAATCTTCGGCATTGACTTCGGTATTTCAATCGATTGTCGATGATGTATTAAGATC

AACCACAGAACAATCGTCAATGAGTTTAGGCATATTGCGACAGATCCAATATGGAGGGTACATCAATAATCCGATGTATTTTCATTTCAGTGT

TTTGTTGTTGTCTAAAATTAGGTCAAACTCGTATCACGAACTTTTTGTTGCATCAGCTCAGAAAAAAAGCTTCAATGAAATATCAAATACTTTG

GAAAAATTGAATCAAGAAATGATGCAGTTGGCAGCTCATTCAGCAGAGGCAATCAAACCAAGATTTCATAATGATTTGAGATTCCAAGTTTCT

GACACAGACAATTCTATTTCAAGAAAAGAGACAATTTTGTCATTCAAGCTTTCATTTTTCTGTCATTTGATGATTATTAATAGATATCCATTTAT

GATTAGTACCAAAGATTCATTATTAGATGATAGAATTTTACAATATAGAAATCTTTCATTAGACTCGGCAAGAACCATTCTTTTGCTTGTCAAA

CTGTGGGATAGATCATCAGCAACGGCGATTTTCTTCAATTGGGCACTTTATTTTCCTGTTGCAGCATTTCTTGTATTATCAGCTGCTATTTTGAA

TCATCCATCATTAGCAGAATCGCAACGAGATTTATACTTGTTGATTGATATTGCTTTATCTTATTTCAGTTGTTCCAATGAATGGAAACATAGT

GATCTGTTCATCAACAAGAAGACAGTCATATATACAAATAAGGCATTGTCGATAGAATTAATTATTAGATTGATGTTAAGGATAGTTATTAAA

GTGTTTGAAACTCAAACTGGTATTTCAATTTTGGACAACAATCAAATTTTGAAAGATTATTTGAAAGAAGCCGAGACAAAGTTTCCTGAAATT

TTCCAGAATCATCAAGAATTCACTTCGCGAATGATGCAGGTAGTTGGTGCGTCGCCATTTGGTAGTTCTGGTGATGAGTATACCAACAAAAGA

ACTGGTGCTAGTCCAAGAAATGCATCAGCATATAGTGCCAAATCTCCTAGTTATAATCCTTCTTTGTCAAATATTATTAATAATGATGTAAATG

GAGTCACAAATGGAAGTTCTGGTAGTGTTACAGGAAGTAGTAATAGTCCAAATAATGGTGTTAATTTGCAACATGCATCAACTCCGAATGGAG

GTATACCCATTTCCAACGGTTATGATTTTCTAAATGAATATGTGGGTGGCGATGCATCGTCGTTACCGTTTGGGCAATTTGATAATTTACCGAA

CTTTTTCTTTGATAATAATCTTGGTGTATAA

UPC2, wild-type

>PQTP01000011.1:341365-343713 Candida tropicalis MYA-3404 tig00000047_pilon, whole genome shotgun sequence

ATGACAGTCAAACAAGAGTCGGCCAATTCAACATTCAATGCCCTCGATATCGCGTTTGGTGAAAATGACGCGTCACTTTCAAAAGCAACCATG

GCTCCATCCATGATTCCTAGAAAACAATCCAAATCATCTACTGGTAAACGAAAATATCATCAAAAATCCAGAAATGGGTGTTCAACCTGTAAA

AGAAGACGTGTCAAATGTGATGAACAAAAACCTGTATGTGGAAACTGTACCAAGTTAAAACTCGACTGTGGTTATCTTCATGTTACAGCAGAT

GATATTGAAGCTAACAAAAAATCAGAAGCTAATGGCCCACAACCAAAGAAGAGAAAGAGAAAATCATCCCTGAGTCTTGATTTACCTATGAG

TGGAACAACAACACAACAAGCAACCCCATCTATGACACCAAGTCCAGAAGCTACCGCCACTACAAATGCTGCCAAGATGAATATCCCTTCTTT

ACCACAATTAAACCCATTAAATGCATTGTCTTCAGGACTTTTAAGTGCAGGGAATTTGAACAATTTGAATATTGCTCATTTGGTGAATAATCTT

TCAGGTTTAGGGGATTTAAGTAATCTCACAAGTCTCGGTAATTTAGCAAGTCTATCGAATTTGGCAACGTTGGCTCAATTACCAATAGATTTGA

GTAATTTGGGTGCTTTGTTGGATCCTCTGATGGCAAACAATCTTGCTGCAACTGCCTTGGGAGGAAATACCCCTACATCCATTCCAACGAATAT

CAACGCTCAACAAAATGGATTTGATTCAAGAAAATCACTGGCAGTATCTGATTTGCAACAATCTTCAATTCAACAACAACAACAACAATCTCA

(28)

GATGCCGCTCCCACCGCAACAGCAACAGCAAGCCCCATCTCAACCACAAGCACAAGCGCAAGCACAATCACAAGCACAATCGCAACCACGTC

CACAACAGCAACAGCAACCACCACCACAGTCACAGCAACAATCACCGACAATGCAAATGGGCAATAGCCCCATTCAACATCACCTTCAACCA

ACATTGGCTTCACAGCTGGATTTGCCGGGAATGAACTATCCAGGATGTACTCCAAGTACGACCACAAGAAATCCTTTTGCAACAGCAGCTTCA

ACTTCTTCAACTAACAATATTGGAACTATGCCTACATCATCTGCTGATGGTACTGCTGGAACCTCAGCGAAATCTATACCTAATATTTCACCGA

ATACTACACATTCTACAAATCCATTGAACAATCCTCTTTCACAAGGAATGCAAACAAGTCTTAATATGCTTGATTTGAAATTAATGTTCCATTA

TACTTCACAGGTTGCGAATACTATCACCGGTGCTGGTATTTCGGAGACTAACATCTGGAACCATGATATTCCATTATTAGCCTTTGAACACCCC

TTTTTAATGCATTCAATATTAGCCTTTAGTGCTACTCACTTGTCAAGAACTGAAAAGGGGTTAGATCAATGTGTTACTTCCCATCGTGGTGATG

CCTTGCGATTATTGCGTGAGGCGGTATTGAATATCAATGCGGATAACACGGACGCATTAGTTGCTAGTGCATTGATCTTAATTATGGATTCATT

GGCAAATGCATCTTTCCCTTCGTCAACATCTCCTAAATCTTTACCTGCTTCTGCATGGATTTTCCATGTTAAAGGTGCAGCCACTATTTTGACTG

CCGTATGGCCATTAACCGAAGCATCCAGATTCTATAAGTTCATTTCAGTTGATTTGGGAGATTTAGGAGATATAATCAACCAAGGAGTCAATT

CAAATAAACCAAAGGGTATTGATCGTGAAGGAGCTTCTTATTACACAGATTTGGAATGTCACGATGCTGATATTGCTGATTTATATCCGGTTA

AGATTGATTCTCCTTATTTAATCACCCTCGCCTATTTGAATAAATTACACAAGGAAAGATACAAGTCTGACTTTATATTACGAATCTTTGCCTTT

CCAGCACTTTTGGACAAACAGTTTATGGCATTATTAATGTCTGGGGACGTCAAGGCTATGAGAATCATGAGAAGCTATTACAAGTTGTTGCGT

TCTTTCACTACTGAAATGAAGGATAAAGTCTGGTTTTTGGAAGGAGTTTCGCTGGTATTACCAGTTAATGTTGAAGAATATGCTGGTGGAGCT

GGAGGTATGCACATGATGATGGATTTCCTTGGTGGAGGGCCAGCGATTATTGATGATCATGAAATTGATAAAGAAATGACGAAATTCGATCC

AAATGGATCACTTACTAATAAATTAATTGATACGAATAATTTACCTAGTGATATAACAAGCAATTTAGATATCATGCAAGGAGATACGGGGTT

CATGAACTTGAAATAG

HS1 of FKS1,

HS1> TTCTTGACTTTGTCTTTAAGAGATCCA

HS2 of FKS1,

HS2> AATCTTTCTCCAGCTGTTGATTGG

(29)

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The research described in this thesis was carried out in the Department of Molecular Microbiology of the Groningen Biomolecular Sciences and Biotechnology Institute