Antibiotic Susceptibility Screening and Search for Resistance Genes in <i>Yersinia pestis</i> Clinical Isolates from Plague Outbreaks in Natural Foci of Kazakhstan (1926–2003)

<b><i>Background:</i></b> Antimicrobial resistance (AMR) is a growing global threat that complicates the treatment of infectious diseases, including plague. <i>Yersinia pestis</i>, the causative agent of plague, remains a serious public health concern in natural foci, such as those in Kazakhstan, where approximately 40% of the territory is plague-endemic. Despite the last reported human case in 2003, data on antibiotic resistance among <i>Y. pestis</i> isolates from these foci, especially historical ones, remain limited. <b><i>Materials and Methods:</i></b> A total of 75 <i>Y. pestis</i> strains were examined, including 61 isolates obtained from patients and deceased individuals during epidemic outbreaks (1926-2003) and 14 isolates from carriers and vectors in natural plague foci. Taxonomic identification was conducted using the Vitek 2 Compact 30 system. Antibiotic susceptibility was assessed by Kirby-Bauer disk diffusion and E-test methods. Extended-spectrum β-lactam (ESBL) activity was evaluated phenotypically, and resistance genes to glycopeptides and β-lactams were screened by real-time polymerase chain reaction (RT-PCR) using the BacResista GLA Detection Kit. <b><i>Results:</i></b> All isolates showed complete susceptibility (100%) to β-lactams, tetracyclines, aminoglycosides, amphenicols, glycopeptides, lincosamides, and quinolones. The overall susceptibility rate across antibiotic classes was 97.5%. Macrolides exhibited low activity (0.0-58.0%), consistent with known limitations against Gram-negative bacteria. No ESBL production was detected phenotypically, and RT-PCR screening found no resistance genes (vanA/B, mecA, tem, ctx-M-1, shv, oxa, imp, kpc, ndm, etc.). <b><i>Conclusions:</i></b> These findings confirm a lack of resistance to key antibiotic classes in historical <i>Y. pestis</i> isolates from Kazakhstan. Despite the absence of recent human cases, ongoing epizootics among wild animals highlight a persistent risk of transmission. This study, conducted for the first time in Kazakhstan, has important implications for public health preparedness and clinical management during plague outbreaks.