Fatal sepsis caused by mecA-positive oxacillin-susceptible Staphylococcus aureus: First report in a tertiary hospital of southern Brazil

Duarte, Felipe Crepaldi; Danelli, Tiago; Tavares, Eliandro Reis; Morguette, Ana Elisa Belotto; Kerbauy, Gilselena; Grion, Cíntia Magalhães Carvalho; Yamauchi, Lucy Megumi; Perugini, Marcia Regina Eches; Yamada‐Ogatta, Sueli Fumie

doi:10.1016/j.jiac.2018.09.010

Cited by 16 publications

(16 citation statements)

References 23 publications

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Section: Discussionmentioning

confidence: 99%

“…These observations suggest that a combination of oxacillin and cefoxitin susceptibility tests, as recommended elsewhere 43 , or detection of mecA will be more reliable for the identification of MRSA. Despite being phenotypically susceptible to oxacillin, β-lactam resistance can easily be induced in OS-MRSA 20,21,44 . The mechanisms regulating oxacillin susceptibility in S. aureus appear to differ depending on the types of mutations and genetic basis of the individual isolates.…”

Section: Discussionmentioning

confidence: 99%

“…It remains to be further studied, however, how this response leads to substantial metabolic changes towards acquisition of the resistance. OS-MRSA is considered problematic in the clinical setting because the strain is prone to develop high-level β-lactam resistance during the course of antibiotic treatment 20,44 . Because the targets of antibiotics are generally essential proteins in bacteria, the acquisition of antibiotic resistance is usually associated with a fitness cost 56 .…”

Section: Discussionmentioning

confidence: 99%

“…Since its first description in 1991, OS-MRSA 15 , 38 , which is related to borderline methicillin-resistant MRSA 39 , has been frequently isolated in hospital and community settings with a prevalence rate of 0.62 – 33.7% 12 , 15 , 18 , 20 , 40 , 41 . The presence of OS-MRSA is currently a challenge in the clinical management of staphylococcal infections and requires great attention because it is prone to be misidentified as MSSA via routine β-lactam susceptibility testing 10 , 12 , 14 .…”

Section: Discussionmentioning

confidence: 99%

“…Owing to its susceptibility to oxacillin, OS-MRSA might be misidentified as methicillin-susceptible S. aureus (MSSA) in routine clinical laboratories in which mecA detection is unavailable 17 . In addition, despite being susceptible to β-lactam antibiotics, OS-MRSA is prone to develop β-lactam resistance following antibiotic therapy due to its carriage of mecA 10 – 12 , 14 , 15 , ultimately leading to β-lactam treatment failure 18 – 20 . Recent findings in study of mechanism of the β-lactam resistance in OS-MRSA include either (1) restoration of frameshift mutation in mecA or (2) mutations in other genes that are not directly relevant to function of mecA 21 – 23 .…”

Section: Introductionmentioning

confidence: 99%

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Identification and characterization of mutations responsible for the β-lactam resistance in oxacillin-susceptible mecA-positive Staphylococcus aureus

Boonsiri

Watanabe

Tan

et al. 2020

Sci Rep

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Staphylococcus aureus strains that are susceptible to the β-lactam antibiotic oxacillin despite carrying mecA (OS-MRSA) cause serious clinical problems globally because of their ability to easily acquire β-lactam resistance. Understanding the genetic mechanism(s) of acquisition of the resistance is therefore crucial for infection control management. For this purpose, a whole-genome sequencing-based analysis was performed using 43 clinical OS-MRSA strains and 100 mutants with reduced susceptibility to oxacillin (MICs 1.0–256 µg/mL) generated from 26 representative OS-MRSA strains. Genome comparison between the mutants and their respective parent strains identified a total of 141 mutations in 46 genes and 8 intergenic regions. Among them, the mutations are frequently found in genes related to RNA polymerase (rpoBC), purine biosynthesis (guaA, prs, hprT), (p)ppGpp synthesis (relSau), glycolysis (pykA, fbaA, fruB), protein quality control (clpXP, ftsH), and tRNA synthase (lysS, gltX), whereas no mutations existed in mec and bla operons. Whole-genome transcriptional profile of the resistant mutants demonstrated that expression of genes associated with purine biosynthesis, protein quality control, and tRNA synthesis were significantly inhibited similar to the massive transcription downregulation seen in S. aureus during the stringent response, while the levels of mecA expression and PBP2a production were varied. We conclude that a combination effect of mecA upregulation and stringent-like response may play an important role in acquisition of β-lactam resistance in OS-MRSA.

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