Genomic diversity of antimicrobial resistance in non-typhoidal Salmonella in Victoria, Australia

Abstract

Non-typhoidal Salmonella (NTS) is the second most common cause of foodborne bacterial gastroenteritis in Australia with antimicrobial resistance (AMR) increasing in recent years. Whole-genome sequencing (WGS) provides opportunities for in silico detection of AMR determinants. The objectives of this study were two-fold: (1) establish the utility of WGS analyses for inferring phenotypic resistance in NTS, and (2) explore clinically relevant genotypic AMR profiles to third generation cephalosporins (3GC) in NTS lineages. The concordance of 2490 NTS isolates with matched WGS and phenotypic susceptibility data against 13 clinically relevant antimicrobials was explored. In silico serovar prediction and typing was performed on assembled reads and interrogated for known AMR determinants. The surrounding genomic context, plasmid determinants and co-occurring AMR patterns were further investigated for multidrug resistant serovars harbouring bla CMY-2, bla CTX-M-55 or bla CTX-M-65. Our data demonstrated a high correlation between WGS and phenotypic susceptibility testing. Phenotypic-genotypic concordance was observed between 2440/2490 (98.0 %) isolates, with overall sensitivity and specificity rates >98 % and positive and negative predictive values >97 %. The most common AMR determinants were bla TEM-1, sul2, tet(A), strA-strB and floR. Phenotypic resistance to cefotaxime and azithromycin was low and observed in 6.2 % (151/2486) and 0.9 % (16/1834) of the isolates, respectively. Several multi-drug resistant NTS lineages were resistant to 3GC due to different genetic mechanisms including bla CMY-2, bla CTX-M-55 or bla CTX-M-65. This study shows WGS can enhance existing AMR surveillance in NTS datasets routinely produced in public health laboratories to identify emerging AMR in NTS. These approaches will be critical for developing capacity to detect emerging public health threats such as resistance to 3GC.

Genomic and Evolutionary Analysis of Salmonella enterica Serovar Kentucky Sequence Type 198 Isolated From Livestock In East Africa

“…No β-lactam resistance genes were detected in two isolates (11586 and 11588) that were phenotypically resistant to ampicillin. Although not frequently observed, similar findings have been recently reported ( Sia et al., 2021 ).…”

“…(2017) . The disagreement between genotypic and phenotypic profiles for aminoglycoside resistance as observed in isolates 11579, 11585, 11586 and 11588 from our study has been previously observed in Salmonella enterica serovars ( Cooper et al., 2020 ; Sia et al., 2021 ). The mechanisms associated with these incongruous findings should be further investigated.…”

Bridging the gap between bioinformatics and the clinical and public health microbiology laboratory: An ISO-accredited genomics workflow for antimicrobial resistance

“…Validation of inferred phenotype against phenotypic AST data demonstrated 98.9% accuracy (95% CI 98.7-99.1%), 98.9% sensitivity (98.4-99.3) and 98.9% specificity (98.7-99.1%) overall (Table 1, Supplementary Table S5 and Figure 6). Accuracy of phenotypic inference was ≥98% for 11/13 antimicrobials (85%), with lower accuracy identified for streptomycin (95.5%, 95% CI 93.7-96.9%) and ciprofloxacin (96.8%, 95% CI 95.4-97.8%), similar to previous findings using different bioinformatic methods 25 .…”

“…8%), similar to previous findings using different bioinformatic methods25 .A number of 'false positive' results were identified for streptomycin (resistant genotype [AMR genes or mutations detected], susceptible phenotype; n=30/716 (4.2%) isolates). The AMR genes detected in phenotypically susceptible isolates were also detected in non-susceptible isolates, although the non-susceptible isolates more often had >1 AMR gene (1 AMR gene, 22% phenotypically resistant; 2 or more AMR genes, 81.4% phenotypically resistant), suggesting that these AMR mechanisms had small but additive effects on phenotype.…”

Drug Resistance due to Elaboration of Beta Lactamases and the Role of CTX-M in Enterobacteriaceae

“…[37][38] This has been recently proved with Carbapenemases in particular with NDM-1 metallo--lactamase producing pathogens. [39][40] However the existence of CTX-M enzymes in animals and food merchandises that are moved among different countries have proposed the likely paths for spread and dispersion. 41 Moreover this rapid dissemination has also been attributed to presence of blaCTX-M of plasmid and transposons, which confer rapid transfer of resistant elements not only within the specie but also to any bacteria it comes in contact to.…”