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Predominance of PVL-negative community-associated methicillin-resistant Staphylococcus aureus sequence type 8 in newly diagnosed HIV-infected adults, Tanzania.

ABSTRACT: Difficult-to-treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are of concern in people living with HIV infection as they are more vulnerable to infection. We aimed to identify molecular characteristics of MRSA colonizing newly diagnosed HIV-infected adults in Tanzania. Individuals newly diagnosed with HIV infection were recruited in Dar es Salaam, Tanzania, from April 2017 to May 2018, as part of the randomized clinical trial CoTrimResist ( ClinicalTrials.gov identifier: NCT03087890). Nasal/nasopharyngeal isolates of Staphylococcus aureus were susceptibility tested by disk diffusion method, and cefoxitin-resistant isolates were characterized by short-reads whole genome sequencing. Four percent (22/537) of patients carried MRSA in the nose/nasopharynx. MRSA isolates were frequently resistant towards gentamicin (95%), ciprofloxacin (91%), and erythromycin (82%) but less often towards trimethoprim-sulfamethoxazole (9%). Seventy-three percent had inducible clindamycin resistance. Erythromycin-resistant isolates harbored ermC (15/18) and LmrS (3/18) resistance genes. Ciprofloxacin resistance was mediated by mutations of the quinolone resistance-determining region (QRDR) sequence in the gyrA (S84L) and parC (S80Y) genes. All isolates belonged to the CC8 and ST8-SCCmecIV MRSA clone. Ninety-five percent of the MRSA isolates were spa-type t1476, and one exhibited spa-type t064. All isolates were negative for Panton-Valentine leucocidin (PVL) and arginine catabolic mobile element (ACME) type 1. All ST8-SCCmecIV-spa-t1476 MRSA clones from Tanzania were unrelated to the globally successful USA300 clone. Carriage of ST8 MRSA (non-USA300) was common among newly diagnosed HIV-infected adults in Tanzania. Frequent co-resistance to non-beta lactam antibiotics limits therapeutic options when infection occurs.

SUBMITTER: Manyahi J

PROVIDER: S-EPMC8206053 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceHousehold environmental surfaces may serve as vectors for the acquisition and spread of methicillin-resistant Staphylococcus aureus (MRSA) among household members, although few studies have evaluated which objects are important reservoirs of MRSA.ObjectivesTo determine the prevalence of environmental MRSA contamination in households of children with MRSA infection; define the molecular epidemiology of environmental, pet, and human MRSA strains within households; and identify factors associated with household MRSA contamination.Design, setting, and participantsFifty children with active or recent culture-positive community-associated MRSA infection were enrolled from 2012 to 2013 at St Louis Children's Hospital and at community pediatric practices affiliated with the Washington University Pediatric and Adolescent Ambulatory Research Consortium in St Louis, Missouri.Main outcomes and measuresSamples of participants' nares, axillae, and inguinal folds were cultured to detect S aureus colonization. Samples of 21 household environmental surfaces, as well as samples obtained from pet dogs and cats, were cultured. Molecular typing of S aureus strains was performed by repetitive-sequence polymerase chain reaction to determine strain relatedness within households.ResultsMethicillin-resistant S aureus was recovered from samples of environmental surfaces in 23 of the 50 households (46%), most frequently from the participant's bed linens (18%), television remote control (16%), and bathroom hand towel (15%). It colonized 12% of dogs and 7% of cats. At least 1 surface was contaminated with a strain type matching the participant's isolate in 20 households (40%). Participants colonized with S aureus had a higher mean (SD) proportion of MRSA-contaminated surfaces (0.15 [0.17]) than noncolonized participants (0.03 [0.06]; mean difference, 0.12 [95% CI, 0.05-0.20]). A greater number of individuals per 1000 ft 2 (93 m2) were also associated with a higher proportion of MRSA-contaminated surfaces (β = 0.34, P = .03). The frequency of cleaning household surfaces was not associated with S aureus environmental contamination.Conclusions and relevanceMethicillin-resistant S aureus strains concordant with infecting and colonizing strains are present on commonly handled household surfaces, a factor that likely perpetuates MRSA transmission and recurrent disease. Future studies are needed to determine methods to eradicate environmental contamination and prevent MRSA transmission in households.

Project description:Methicillin resistant Staphylococcus aureus (MRSA) infection is becoming refractory to existing antibiotic therapy owing to the inherent ability of S. aureus to develop rapid resistance and is considered a major threat to public health. We found that a natural isolate of Bacillus pumilus from the Columbia River Estuary produces a strong anti-MRSA compound, amicoumacin A. As amicoumacin A has been reported to exhibit anti-microbial, anti-inflammatory, and anti-ulcer activities, we sought to uncover its mechanism of action. Genome-wide transcriptome analysis of S. aureus COL in response to amicoumacin A showed alteration in the expression of genes involved in several cellular processes including cell envelope turnover, cross-membrane transport, virulence, metabolism, and general stress response. The most highly induced gene was lrgA, encoding an antiholin-like product, which has been shown to be induced in response to a collapse of membrane potential. In order to gain further insight into the mechanism of action of amicoumacin A, a whole genome comparison of wild-type COL and amicoumacin A-resistant mutants isolated by serial passage method was carried out. Single point mutations resulting in codon substitutions were uncovered in several distinct genes: ksgA, RNA dimethyltranferase; fusA, elongation factor G; dnaG, primase, ; lacD, tagatose 1,6-bisphosphate aldolase, ; and SACOL0611, encoding a putative glycosyl transferase gene. Based on these results, a candidate approach was undertaken to recreate the same amino acid substitution individually in FusA and KsgA, each of which resulted in two-fold resistance towards amicoumacin A. The fusA gene is known as the site for fusidic acid- resistant mutations; however the codon substitutions in EF-G that cause amicoumacin A resistance and fusidic acid resistance occur in separate domains and do not bring about cross resistance. Taken together, these results suggest that amicoumacin A might cause perturbation of the cell membrane and lead to energy dissipation. Decreased rates of cellular metabolism including protein synthesis and DNA replication in resistant strains might allow cells to compensate for membrane dysfunction and thus increase cell survivability.

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Predominance of PVL-negative community-associated methicillin-resistant Staphylococcus aureus sequence type 8 in newly diagnosed HIV-infected adults, Tanzania.

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