Thymidine‐auxotrophic Staphylococcus aureus small‐colony variant bacteremia in a patient with cystic fibrosis

Thymidine‐auxotrophic Staphylococcus aureus small‐colony variant bacteremia in a patient with cystic fibrosis

Background Small‐colony variants (SCVs) are a morphologic subtype of Staphylococcus aureus that may occur through several mechanisms including auxotrophism for thymidine, hemin, or menadione. Auxotrophic SCV for thymidine fail to synthesize DNA specifically because of mutations in the thymidylate sy...

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Bibliographic Details
Published in:Pediatric pulmonology Vol. 55; no. 6; pp. 1388 - 1393
Main Authors: Souza, Dilair C., Cogo, Laura L., Palmeiro, Jussara K., Dalla‐Costa, Libera M., Oliveira Tomaz, Ana P., Riedi, Carlos A., Rosario Filho, Nelson A.
Format: Journal Article
Language:English
Published: United States Wiley Subscription Services, Inc 01-06-2020
Subjects:
auxotrophism
Binding sites
Cystic fibrosis
Genes
Mutation
SCVs
Staphylococcus infections
thyA
thymidine‐dependent
thymidine-dependent
thyA
SCVs
auxotrophism
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Summary:Background Small‐colony variants (SCVs) are a morphologic subtype of Staphylococcus aureus that may occur through several mechanisms including auxotrophism for thymidine, hemin, or menadione. Auxotrophic SCV for thymidine fail to synthesize DNA specifically because of mutations in the thymidylate synthase gene. We isolated S. aureus thymidine‐dependent SCVs (TD‐SCV) from blood and respiratory samples of a pediatric patient with cystic fibrosis and pulmonary exacerbation. Methods Nutritional dependence of SCVs on hemin, menadione, and thymidine was evaluated. Antimicrobial susceptibility testing was performed through broth microdilution. Polymerase chain reaction was carried out for mecA, ermA, ermB, ermC, msrA, and msrB resistance genes. DNA sequencing was used to determine mutations in thyA and the multilocus sequence typing to identify genetic relatedness. Results Methicillin‐sensitive S. aureus with normal and TD‐SCV phenotypes were isolated from respiratory samples and a TD‐SCV phenotype was isolated from blood culture. Macrolides resistance was attributed to ermC and msrB genes. All isolates belonged to ST398. The thyA gene in S. aureus is 957 nucleotides in length and encodes a protein of 318 amino acids. The TD‐SCV isolates carried a −2 nt frameshift mutation (delta 667GC668) in thyA, creating a stop codon at residue 222 close to the predicted binding site for deoxyuridine monophosphate. Conclusions The pathogenesis of SCVs is complex and not fully elucidated. Factors inherent to the patient such as physiological conditions, recurrent infections, or coinfection should be considered. Although SCVs are considered less virulent, they showed the ability to invade and cause bacteremia in the patient.
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ISSN:8755-6863
1099-0496
DOI:10.1002/ppul.24730