Understanding Klebsiella pneumoniae clonality, virulence and antimicrobial resistance at the human-animal-environment interface from Bangladesh

Thesis

The One Health approach is increasingly recognised as crucial to addressing the global threat of antimicrobial resistance (AMR). However, data on the epidemiology of AMR at the human-animal-environmental interface remain limited from low- and middle-income countries. This thesis presents the first systematic One Health survey of Klebsiella pneumoniae and related species in Bangladesh, integrating phenotypic and genomic analyses with clinical and demographic metadata.

A total of 3759 samples were collected between December 2021 and March 2023 from humans (urinary tract infections, surgical site infections, and healthy rectal carriage), livestock (chicken, domestic animals, free-flying birds) and environmental sources (water and flies) in Mymensingh, Bangladesh. K. pneumoniae was isolated from 14.4% (541/3759) of samples, with marked variation across sources and higher isolation rates during warmer and wetter seasons. Notably, flies showed the highest prevalence (36.4%, 80/220), with significant carriage during summer and monsoon, highlighting their potential as mechanical vectors.

Hospital settings were hotspots for AMR, particularly for extended-spectrum β-lactamase (predominantly bla_CTX–M–15) and carbapenemase (predominantly bla_NDM–5) producers, especially in hospital-associated surgical site infections (SSIs). Convergent multidrug-resistant (MDR) hypervirulent strains, including carbapenem-resistant hypervirulent K. pneumoniae, were restricted to SSIs, representing an acute clinical threat. Clonal dissemination of MDR K. pneumoniae ST48 and ST490 indicated potential outbreak dynamics within surgical wards.

Although overall prevalence was low, plasmid-mediated mobile colistin resistance (mainly mcr-8) was detected in poultry-associated settings, including isolates from flies, water, and healthy humans, but not in clinical isolates. Conversely, carbapenemase genes were rarely identified outside hospitals. Non-pneumoniae Klebsiella species comprised 56.6% (705/1246) of isolates. Despite species diversity, they generally exhibited low levels of AMR and virulence.

While AMR-associated genes were sporadically identified in community and environmental sources, ESBLs, carbapenemases, and hypervirulence determinants were predominantly detected in hospital settings. Collectively, these findings highlight hospitals as critical intervention points to interrupt the dissemination of AMR in Klebsiella and support periodic surveillance across farms, wastewater, and vectors to detect emerging resistance and track high-risk genes within a One Health framework.

Authors: Rahman, S

• DOI: 10.5287/ora-mnz68xn78
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: Bangladesh; Klebsiella pneumoniae; One Health; antimicrobial resistance; virulence; genomic epidemiology
• Subjects: Multidrug resistance; Drug resistance in microorganisms; Klebsiella; Microbiology