Dataset Information

Polymyxin Resistance in Salmonella: Exploring Mutations and Genetic Determinants of Non-Human Isolates.

ABSTRACT: Until 2015, polymyxin resistance was primarily attributed to chromosomal mutations. However, with the first report of mobile colistin resistance (mcr-1) in commensal Escherichia coli from food animals in China, the landscape has changed. To evaluate the presence of polymyxin resistance in Salmonella spp., a drop screening test for colistin and polymyxin B was carried out on 1156 isolates of non-human origin (animals, food, and the environment), received in Brazil, between 2016 and 2021. Subsequently, 210 isolates with resistant results in the drop test were subjected to the gold-standard test (broth microdilution) for both colistin and polymyxin B. Whole-genome sequencing (WGS) of 102 resistant isolates was performed for a comprehensive analysis of associated genes. Surprisingly, none of the isolates resistant to colistin in the drop test harbored any of the mcr variants (mcr-1 to mcr-10). WGS identified that the most common mutations were found in pmrA (n= 22; T89S) and pmrB (n = 24; M15T, G73S, V74I, I83A, A111V). Other resistance determinants were also detected, such as the aac(6')-Iaa gene in 72 isolates, while others carried beta-lactamase genes (bla_TEM-1bla_CTX-M-2, bla_CMY-2). Additionally, genes associated with fluoroquinolone resistance (qnrB19, qnrS1, oqxA/B) were detected in 11 isolates. Colistin and polymyxin B resistance were identified among Salmonella from non-human sources, but not associated with the mcr genes. Furthermore, the already-described mutations associated with polymyxin resistance were detected in only a small number of isolates, underscoring the need to explore and characterize unknown genes that contribute to resistance.

SUBMITTER: Vieira T

PROVIDER: S-EPMC10885896 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Polymyxin Resistance in Salmonella: Exploring Mutations and Genetic Determinants of Non-Human Isolates.

Vieira Thais T Dos Santos Carla Adriana CA de Jesus Bertani Amanda Maria AM Costa Gisele Lozano GL Campos Karoline Rodrigues KR Sacchi Cláudio Tavares CT Cunha Marcos Paulo Vieira MPV Carvalho Eneas E da Costa Alef Janguas AJ de Paiva Jacqueline Boldrin JB Rubio Marcela da Silva MDS Camargo Carlos Henrique CH Tiba-Casas Monique Ribeiro MR

Antibiotics (Basel, Switzerland) 20240123 2

Until 2015, polymyxin resistance was primarily attributed to chromosomal mutations. However, with the first report of mobile colistin resistance (mcr-1) in commensal Escherichia coli from food animals in China, the landscape has changed. To evaluate the presence of polymyxin resistance in Salmonella spp., a drop screening test for colistin and polymyxin B was carried out on 1156 isolates of non-human origin (animals, food, and the environment), received in Brazil, between 20 ...[more]

PMID: 38391496

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Project description:Salmonella genomic island 1 (SGI1) contains a multidrug resistance region conferring the ampicillin-chloramphenicol-streptomycin-sulfamethoxazole-tetracycline resistance phenotype encoded by bla(PSE-1), floR, aadA2, sul1, and tet(G). Its increasing spread via interbacterial transfer and the emergence of new variants are important public health concerns. We investigated the molecular properties of SGI1-carrying Salmonella enterica serovars selected from a European strain collection. A total of 38 strains belonging to S. enterica serovar Agona, S. enterica serovar Albany, S. enterica serovar Derby, S. enterica serovar Kentucky, S. enterica serovar Newport, S. enterica serovar Paratyphi B dT+, and S. enterica serovar Typhimurium, isolated between 2002 and 2006 in eight European countries from humans, animals, and food, were subjected to antimicrobial susceptibility testing, molecular typing methods (XbaI pulsed-field gel electrophoresis [PFGE], plasmid analysis, and multilocus variable-number tandem-repeat analysis [MLVA]), as well as detection of resistance and virulence determinants (PCR/sequencing and DNA microarray analysis). Typing experiments revealed wide heterogeneity inside the strain collection and even within serovars. PFGE analysis distinguished a total of 26 different patterns. In contrast, the characterization of the phenotypic and genotypic antimicrobial resistance revealed serovar-specific features. Apart from the classical SGI1 organization found in 61% of the strains, seven different variants were identified with antimicrobial resistance properties associated with SGI1-A (S. Derby), SGI1-C (S. Derby), SGI1-F (S. Albany), SGI1-L (S. Newport), SGI1-K (S. Kentucky), SGI1-M (S. Typhimurium), and, eventually, a novel variant similar to SGI1-C with additional gentamicin resistance encoded by aadB. Only minor serovar-specific differences among virulence patterns were detected. In conclusion, the SGI1 carriers exhibited pathogenetic backgrounds comparable to the ones published for susceptible isolates. However, because of their multidrug resistance, they may be more relevant in clinical settings.

Project description:Infection with P. aeruginosa, one of the most relevant opportunistic pathogens in hospital-acquired infections, can lead to high mortality due to its low antibiotic susceptibility to limited choices of antibiotics. Polymyxin as last-resort antibiotics is used in the treatment of systemic infections caused by multidrug-resistant P. aeruginosa strains, so studying the emergence of polymyxin-resistant was a must. The present study was designed to define genomic differences between paired polymyxin-susceptible and polymyxin-resistant P. aeruginosa strains and established polymyxin resistance mechanisms, and common chromosomal mutations that may confer polymyxin resistance were characterized. A total of 116 CRPA clinical isolates from patients were collected from three tertiary care hospitals in China during 2017-2021. Our study found that polymyxin B resistance represented 3.45% of the isolated carbapenem-resistant P. aeruginosa (CRPA). No polymyxin-resistant isolates were positive for mcr (1-8 and 10) gene and efflux mechanisms. Key genetic variations identified in polymyxin-resistant isolates involved missense mutations in parR, parS, pmrB, pmrA, and phoP. The waaL and PA5005 substitutions related to LPS synthesis were detected in the highest levels of resistant strain (R1). The missense mutations H398R in ParS (4/4), Y345H in PmrB (4/4), and L71R in PmrA (3/4) were the predominant. Results of the PCR further confirmed that mutation of pmrA, pmrB, and phoP individually or simultaneously did affect the expression level of resistant populations and can directly increase the expression of arnBCADTEF operon to contribute to polymyxin resistance. In addition, we reported 3 novel mutations in PA1945 (2129872_A < G, 2130270_A < C, 2130272_T < G) that may confer polymyxin resistance in P. aeruginosa. Our findings enriched the spectrum of chromosomal mutations, highlighted the complexity at the molecular level, and multifaceted interplay mechanisms underlying polymyxin resistance in P. aeruginosa.

Dataset Information

Polymyxin Resistance in Salmonella: Exploring Mutations and Genetic Determinants of Non-Human Isolates.

Publications

Polymyxin Resistance in <i>Salmonella</i>: Exploring Mutations and Genetic Determinants of Non-Human Isolates.

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