Molecular characterization of methicillin-resistant Staphylococcus aureus isolated from a Brazilian university hospital

Martins, André; Riboli, Danilo Flávio Moraes; Pereira, Valéria Cataneli; Cunha, Maria de Lourdes Ribeiro de Souza da

doi:10.1016/j.bjid.2013.11.003

Cited by 12 publications

(10 citation statements)

References 27 publications

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“…In this study, Debio1452 was shown to have significant activity against a diverse collection of staphylococcal pathogens, including MRSA strains that are endemic in hospital and community environments worldwide (18,(27)(28)(29)(30) (9). This indicated that the activity of Debio1452 tested against isolates collected from various regions of the world was similar to that noted in the previously conducted Canadian studies (9,10).…”

Section: Discussionsupporting

confidence: 72%

Activity of Debio1452, a FabI Inhibitor with Potent Activity against Staphylococcus aureus and Coagulase-Negative Staphylococcus spp., Including Multidrug-Resistant Strains

Flamm

Rhomberg

Kaplan³

et al. 2015

Antimicrob Agents Chemother

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Staphylococcus aureus and coagulase-negative staphylococci (CoNS) are responsible for a wide variety of human infections. The investigational antibacterial Debio1450 (previously AFN-1720), a prodrug of Debio1452 (previously AFN-1252), specifically targets staphylococci without significant activity against other Gram-positive or Gram-negative species. Debio1452 inhibits FabI, an enzyme critical to fatty acid biosynthesis in staphylococci. The activity of Debio1452 against CoNS, methicillin-susceptible S. aureus (MSSA), and methicillin-resistant S. aureus (MRSA), including significant clones, was determined. A globally diverse collection of 574 patient isolates from 35 countries was tested that included CoNS (6 species, 103 strains), MSSA (154 strains), MRSA (163 strains), and molecularly characterized strains (including spa-typed MRSA clones; 154 strains). The isolates were tested for susceptibility by CLSI broth microdilution methods against Debio1452 and 10 comparators. The susceptibility rates for the comparators were determined using CLSI and EUCAST breakpoint criteria. All S. aureus and CoNS strains were inhibited by Debio1452 concentrations of <0.12 and <0.5 g/ml, respectively. The MIC 50 s for MSSA, MRSA, and molecularly characterized MRSA strains were 0.004 g/ml, and the MIC 90 s ranged from 0.008 to 0.03 g/ml. The MICs were higher for the CoNS isolates (MIC 50/90 , 0.015/0.12 g/ml). Among S. aureus strains, resistance was common for erythromycin (61.6%), levofloxacin (49.0%), clindamycin (27.6%), tetracycline (15.7%), and trimethoprim-sulfamethoxazole (7.0%). Debio1452 demonstrated potent activity against MSSA, MRSA, and CoNS. Debio1452 showed significantly greater activity overall (MIC 50 , 0.004 g/ml) than the other agents tested against these staphylococcal species, which included dominant MRSA clones and strains resistant to currently utilized antimicrobial agents. Inhibitors of the fatty acid biosynthetic pathway have emerged as part of a potential approach to developing antibacterial agents (1-6). Among those inhibitors, Debio1452 (previously designated AFN-1252) was characterized for its specific activity against FabI, an essential enzyme involved in the final step of the elongation cycle of bacterial fatty acid biosynthesis (7,8). Debio1452 is a novel FabI inhibitor that specifically targets Staphylococcus species (7)(8)(9)(10)(11). This compound has demonstrated a lack of activity against other species of bacteria, including streptococci, enterococci, Enterobacteriaceae, and nonfermentative Gram-negative species (9, 11).The narrow targeted spectrum (staphylococci) exhibited by Debio1452 provides the benefit of minimizing the effect on normal bacterial flora and hence the potential for reduced antibioticassociated adverse events, such as overgrowth of resistant commensals, diarrhea, and candidiasis. Further, its unique mode of action lessens the likelihood that resistance development to Debio1452 would lead to cross-resistance with currently available antimicrobial agents. A phase 2a study has be...

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Section: Discussionsupporting

confidence: 72%

Activity of Debio1452, a FabI Inhibitor with Potent Activity against Staphylococcus aureus and Coagulase-Negative Staphylococcus spp., Including Multidrug-Resistant Strains

Flamm

Rhomberg

Kaplan³

et al. 2015

Antimicrob Agents Chemother

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“…As such, numerous studies have been undertaken to elucidate the genetics of S. aureus including genes that confer resistance to antibiotics, heavy metals as well as virulence genes. MRSA strains are major health threat and were isolated from infected patients, livestock, aquatic products, different environmental sources including wastewater [39,68,69]. The predominant target gene to be screened to detect methicillin resistance is mecA, however, numerous studies have reported S. aureus isolates that exhibited phenotypic resistance to methicillin but were found to be negative for the mecA gene [70,71,72].…”

Section: Discussionmentioning

confidence: 99%

Isolation and Molecular Identification of Virulence, Antimicrobial and Heavy Metal Resistance Genes in Livestock-Associated Methicillin-Resistant Staphylococcus aureus

2019

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Staphylococcus aureus is one of the most important pathogens of humans and animals. Livestock production contributes a significant proportion to the South African Gross Domestic Product. Consequently, the aim of this study was to determine for the first time the prevalence, virulence, antibiotic and heavy metal resistance in livestock-associated S. aureus isolated from South African livestock production systems. Microbial phenotypic methods were used to detect the presence of antibiotic and heavy metal resistance. Furthermore, molecular DNA based methods were used to genetically determine virulence as well as antibiotic and heavy metal resistance determinants. Polymerase chain reaction (PCR) confirmed 217 out of 403 (53.8%) isolates to be S. aureus. Kirby-Bauer disc diffusion method was conducted to evaluate antibiotic resistance and 90.8% of S. aureus isolates were found to be resistant to at least three antibiotics, and therefore, classified as multidrug resistant. Of the antibiotics tested, 98% of the isolates demonstrated resistance towards penicillin G. High resistance was shown against different heavy metals, with 90% (196/217), 88% (192/217), 86% (188/217) and 84% (183/217) of the isolates resistant to 1500 µg/mL concentration of Cadmium (Cd), Zinc (Zn), Lead (Pb) and Copper (Cu) respectively. A total of 10 antimicrobial resistance and virulence genetic determinants were screened for all livestock associated S. aureus isolates. Methicillin-resistant S. aureus (MRSA) isolates were identified, by the presence of mecC, in 27% of the isolates with a significant relationship (p < 0.001)) with the host animal. This is the first report of mecC positive LA-MRSA in South Africa and the African continent. The gene for tetracycline resistance (tetK) was the most frequently detected of the screened genes with an overall prevalence of 35% and the highest prevalence percentage was observed for goats (56.76%) followed by avian species (chicken, duck and wild birds) (42.5%). Virulence-associated genes were observed across all animal host species. The study reports the presence of luks/pv, a gene encoding the PVL toxin previously described to be a marker for community acquired-MRSA, suggesting the crossing of species between human and livestock. The high prevalence of S. aureus from the livestock indicates a major food security and healthcare threat. This threat is further compounded by the virulence of the pathogen, which causes numerous clinical manifestations. The phenomenon of co-selection is observed in this study as isolates exhibited resistance to both antibiotics and heavy metals. Further, all the screened antibiotic and heavy metal resistance genes did not correspond with the phenotypic resistance.

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“…The isolates of the ST239(CC8)-SCC mec III lineage—one of the most largely disseminated healthcare-associated MRSA (HA-MRSA)—are endemic in several hospitals and have been described in outbreaks around the world (Li et al 2012; Figueiredo and Ferreira 2014; Baines et al 2015). In Brazil, MRSA isolates of a multiresistant S. aureus clone—the Brazilian epidemic clone (BEC) of the lineage ST239-SCC mec III—are disseminated in hospitals of different regions (Teixeira et al 1995; Campos et al 2012; Martins et al 2014). However, the factors involved in the predominance of a MRSA clone over another remains unclear (Figueiredo and Ferreira 2014).…”

Section: Introductionmentioning

confidence: 99%

Complete Genome Sequence of the MRSA Isolate HC1335 from ST239 Lineage Displaying a Truncated AgrC Histidine Kinase Receptor

et al. 2016

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Methicillin-resistant Staphylococcus aureus (MRSA) is still one of the most important hospital pathogen globally. The multiresistant isolates of the ST239-SCCmecIII lineage are spread over large geographic regions, colonizing and infecting hospital patients in virtually all continents. The balance between fitness (adaptability) and virulence potential is likely to represent an important issue in the clonal shift dynamics leading the success of some specific MRSA clones over another. The accessory gene regulator (agr) is the master quorum sensing system of staphylococci playing a role in the global regulation of key virulence factors. Consequently, agr inactivation in S. aureus may represent a significant mechanism of genetic variability in the adaptation of this healthcare-associated pathogen. We report here the complete genome sequence of the methicillin-resistant S. aureus, isolate HC1335, a variant of the ST239 lineage, which presents a natural insertion of an IS256 transposase element in the agrC gene encoding AgrC histidine kinase receptor.

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Molecular characterization of methicillin-resistant Staphylococcus aureus isolated from a Brazilian university hospital

Cited by 12 publications

References 27 publications

Activity of Debio1452, a FabI Inhibitor with Potent Activity against Staphylococcus aureus and Coagulase-Negative Staphylococcus spp., Including Multidrug-Resistant Strains

Activity of Debio1452, a FabI Inhibitor with Potent Activity against Staphylococcus aureus and Coagulase-Negative Staphylococcus spp., Including Multidrug-Resistant Strains

Isolation and Molecular Identification of Virulence, Antimicrobial and Heavy Metal Resistance Genes in Livestock-Associated Methicillin-Resistant Staphylococcus aureus

Complete Genome Sequence of the MRSA Isolate HC1335 from ST239 Lineage Displaying a Truncated AgrC Histidine Kinase Receptor

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