Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2019

Host adaptation and convergent evolution increases antibiotic resistance without loss of virulence in a major human pathogen (#271)

Alicia Fajardo-Lubian 1 , Nouri L Ben Zakour 1 , Alex Agyekum 1 , Qin Qi 1 , Jonathan R Iredell 1
  1. The University of Sydney and The Westmead Institute for Medical Research, Westmead, NSW, Australia

As human population density and antibiotic exposure increase, specialised bacterial subtypes have begun to emerge. Arising among species that are common commensals and infrequent pathogens, antibiotic-resistant ‘high-risk clones’ have evolved to better survive in the modern human. Klebsiella pneumoniae is a Gram-negative enteric bacterium and a significant cause of human disease. It is a frequent agent of pneumonia, and systemic infections can have high mortality rates (60%). OmpK35 and OmpK36 are the major co-regulated outer membrane porins of Kpneumoniae. OmpK36 absence has been related to antibiotic resistance but also decreased bacterial fitness and diminished virulence. A mutation that constricts the porin channel (Gly134Asp135 duplication in loop 3 of the porin, OmpK36GD) has been previously observed and suggested as a solution to the fitness cost imposed by loss of OmpK36. In the present study we constructed isogenic mutants to verify this and test the impact of these porin changes on antimicrobial resistance, fitness and virulence. Here, we show that the major matrix porin (OmpK35) of K. pneumoniae is not required in the mammalian host for colonisation, pathogenesis, nor for antibiotic resistance, and that it is commonly absent in pathogenic isolates. This is found in association with, but apparently independent of, a highly specific change (OmpK36GD) in the co-regulated partner porin, the osmoporin (OmpK36), which provides enhanced antibiotic resistance without significant loss of fitness in the mammalian host. These features are common in well-described ‘high-risk clones’ of Kpneumoniae, as well as in unrelated members of this species and similar adaptations are found in other members of the Enterobacteriaceae that share this lifestyle. Available sequence data indicate evolutionary convergence, with implications for the spread of lethal antibiotic-resistant pathogens in humans. Our data provide evidence of specific variations in OmpK36 and the absence of OmpK35 in Kpneumoniae clinical isolates that are examples of successful adaptation to human colonization/infection and antibiotic pressure, and are features of a fundamental evolutionary shift in this important human pathogen. (PlosPathogens, 2019)