103 Linezolid resistance in methicillin-resistant small colony variant Staphylococcus aureus (MRSA-SCV) isolated from cystic fibrosis (CF) patients

One of the most interesting features of Staphylococcus aureus is its ability to switch to a small colony variant (SCV). This switch allows the pathogen to survive periods of antibiotic treatment or pressure from the immune system of the host and further enables it to start the infection once again after the environmental stress declines. However, so far only little is known about this reversion back to the more virulent wild type phenotype. Therefore, this study aimed to analyze the frequency of reversion to the wild type phenotype of thymidine auxotroph S. aureus SCV isolates (TD-SCVs) obtained from patients with cystic fibrosis (CF). With the use of single cell starting cultures, the occurrence of the thymidine prototroph revertants was monitored. The underlying mutational cause of the SCVs and subsequent revertants were analyzed by sequencing the gene coding for thymidylate synthase (ThyA), whose mutations are known to produce thymidine auxotroph S. aureus SCV. In our study, the underlying mutational cause for the switch to the TD-SCV phenotype was primarily point mutations. Out of twelve isolates, seven isolates showed an occurrence of revertants with a frequency ranging from 90.06% to 0.16%. This high variability in the frequency of reversion to the wild type was not expected. However, this variability in the frequency of reversion may also be the key to successful re-infection of the host. Sometimes quick reversion to the wild type proves necessary for survival, whereas other times, staying hidden for a bit longer leads to success in re-colonization of the host.

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A Comparison of the Ultrastructure of the Small-Colony Variant and the Parent Strain of Methicillin-Resistant Staphylococcus aureus

The Journal of Infectious Diseases ◽

10.1093/infdis/125.1.1 ◽

1972 ◽

Vol 125 (1) ◽

pp. 1-4 ◽

Cited By ~ 1

Author(s):

R. J. Bulger ◽

M. Collman ◽

P. Feigl ◽

R. E. Bulger

Keyword(s):

Staphylococcus Aureus ◽

Parent Strain ◽

Methicillin Resistant Staphylococcus Aureus ◽

Methicillin Resistant ◽

Small Colony Variant ◽

Small Colony

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Intracellular Activity of Antibiotics in a Model of Human THP-1 Macrophages Infected by a Staphylococcus aureus Small-Colony Variant Strain Isolated from a Cystic Fibrosis Patient: Pharmacodynamic Evaluation and Comparison with Isogenic Normal-Phenotype and Revertant Strains

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01145-08 ◽

2009 ◽

Vol 53 (4) ◽

pp. 1434-1442 ◽

Cited By ~ 33

Author(s):

Hoang Anh Nguyen ◽

Olivier Denis ◽

Anne Vergison ◽

Anne Theunis ◽

Paul M. Tulkens ◽

...

Keyword(s):

Cystic Fibrosis ◽

Staphylococcus Aureus ◽

Cystic Fibrosis Patient ◽

Similar Reduction ◽

Small Colony Variant ◽

Normal Phenotype ◽

Intracellular Activity ◽

Static Effect ◽

Small Colony ◽

Confocal And Electron Microscopy

ABSTRACT Small-colony variant (SCV) strains of Staphylococcus aureus show reduced antibiotic susceptibility and intracellular persistence, potentially explaining therapeutic failures. The activities of oxacillin, fusidic acid, clindamycin, gentamicin, rifampin, vancomycin, linezolid, quinupristin-dalfopristin, daptomycin, tigecycline, moxifloxacin, telavancin, and oritavancin have been examined in THP-1 macrophages infected by a stable thymidine-dependent SCV strain in comparison with normal-phenotype and revertant isogenic strains isolated from the same cystic fibrosis patient. The SCV strain grew slowly extracellularly and intracellularly (1- and 0.2-log CFU increase in 24 h, respectively). In confocal and electron microscopy, SCV and the normal-phenotype bacteria remain confined in acid vacuoles. All antibiotics tested, except tigecycline, caused a net reduction in bacterial counts that was both time and concentration dependent. At an extracellular concentration corresponding to the maximum concentration in human serum (total drug), oritavancin caused a 2-log CFU reduction at 24 h; rifampin, moxifloxacin, and quinupristin-dalfopristin caused a similar reduction at 72 h; and all other antibiotics had only a static effect at 24 h and a 1-log CFU reduction at 72 h. In concentration dependence experiments, response to oritavancin was bimodal (two successive plateaus of −0.4 and −3.1 log CFU); tigecycline, moxifloxacin, and rifampin showed maximal effects of −1.1 to −1.7 log CFU; and the other antibiotics produced results of −0.6 log CFU or less. Addition of thymidine restored intracellular growth of the SCV strain but did not modify the activity of antibiotics (except quinupristin-dalfopristin). All drugs (except tigecycline and oritavancin) showed higher intracellular activity against normal or revertant phenotypes than against SCV strains. The data may help rationalizing the design of further studies with intracellular SCV strains.

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Frequency of small-colony variants and antimicrobial susceptibility of methicillin-resistant Staphylococcus aureus in cystic fibrosis patients

Diagnostic Microbiology and Infectious Disease ◽

10.1016/j.diagmicrobio.2017.11.012 ◽

2018 ◽

Vol 90 (4) ◽

pp. 296-299 ◽

Cited By ~ 13

Author(s):

Nuntra Suwantarat ◽

Mayer Rubin ◽

Latetia Bryan ◽

Tsigereda Tekle ◽

Michael P. Boyle ◽

...

Keyword(s):

Cystic Fibrosis ◽

Staphylococcus Aureus ◽

Antimicrobial Susceptibility ◽

Methicillin Resistant Staphylococcus Aureus ◽

Methicillin Resistant ◽

Small Colony Variants ◽

Small Colony

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Evolution of Staphylococcus aureus under Vancomycin Selective Pressure: the Role of the Small-Colony Variant Phenotype

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.04508-14 ◽

2014 ◽

Vol 59 (2) ◽

pp. 1347-1351 ◽

Cited By ~ 14

Author(s):

Justin R. Lenhard ◽

Christof von Eiff ◽

Irene S. Hong ◽

Patricia N. Holden ◽

Michael D. Bear ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Antibiotic Therapy ◽

Selective Pressure ◽

Type Model ◽

Methicillin Resistant ◽

Small Colony Variants ◽

Content Type ◽

Small Colony Variant ◽

Small Colony

ABSTRACTStaphylococcus aureussmall-colony variants (SCVs) often persist despite antibiotic therapy. Against a 108-CFU/ml methicillin-resistantS. aureus(MRSA) (strain COL) population of which 0%, 1%, 10%, 50%, or 100% was an isogenichemBknockout (Ia48) subpopulation displaying the SCV phenotype, vancomycin achieved maximal reductions of 4.99, 5.39, 4.50, 3.28, and 1.66 log10CFU/ml over 48 h. Vancomycin at ≥16 mg/liter shifted a population from 50% SCV cells at 0 h to 100% SCV cells at 48 h, which was well characterized by a Hill-type model (R2> 0.90).

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