Colonization and immune modulation properties of Klebsiella pneumoniae biofilm-dispersed cells

Cyril Guilhen,Laura Joseph,Nicolas Charbonnel,Sylvie Miquel,Damien Balestrino,Guillaume Carrier,Christiane Forestier

doi:10.1038/s41522-019-0098-1

Abstract

Biofilm-dispersal is a key determinant for further dissemination of biofilm-embedded bacteria. Recent evidence indicates that biofilm-dispersed bacteria have transcriptional features different from those of both biofilm and planktonic bacteria. In this study, the in vitro and in vivo phenotypic properties of Klebsiella pneumoniae cells spontaneously dispersed from biofilm were compared with those of planktonic and sessile cells. Biofilm-dispersed cells, whose growth rate was the same as that of exponential planktonic bacteria but significantly higher than those of sessile and stationary planktonic forms, colonized both abiotic and biotic surfaces more efficiently than their planktonic counterparts regardless of their initial adhesion capabilities. Microscopy studies suggested that dispersed bacteria initiate formation of microcolonies more rapidly than planktonic bacteria. In addition, dispersed cells have both a higher engulfment rate and better survival/multiplication inside macrophages than planktonic cells and sessile cells. In an in vivo murine pneumonia model, the bacterial load in mice lungs infected with biofilm-dispersed bacteria was similar at 6, 24 and 48 h after infection to that of mice lungs infected with planktonic or sessile bacteria. However, biofilm-dispersed and sessile bacteria trend to elicit innate immune response in lungs to a lesser extent than planktonic bacteria. Collectively, the findings from this study suggest that the greater ability of K. pneumoniae biofilm-dispersed cells to efficiently achieve surface colonization and to subvert the host immune response confers them substantial advantages in the first steps of the infection process over planktonic bacteria.

Highlights

Klebsiella pneumoniae is an opportunist pathogen ubiquitous in nature and found asymptomatically in more than 40% of the population.[1]
Data from our study showed that K. pneumoniae biofilmdispersed bacteria had enhanced colonization capabilities, i.e., adhesion coupled with bacterial multiplication on a substratum, on both biotic and abiotic surfaces
These properties could be due to high metabolic activity but K. pneumoniae dispersed bacteria had growth and ATP content similar to those of planktonic bacteria, as previously observed with S. pneumoniae.[18]

Summary

Introduction

Klebsiella pneumoniae is an opportunist pathogen ubiquitous in nature and found asymptomatically in more than 40% of the population.[1] It has been identified as a direct menace for human health owing to its capacity to resist many antibiotics,[2,3,4] and its pivotal role in the initial acquisition and spreading of antibioticresistant genes.[5] The high ability of K. pneumoniae to form biofilm and to colonize tissues and medical devices is a main factor contributing to the development of healthcare-associated infections.[6,7] The formation of biofilms on respiratory devices can lead to pneumonia via bacterial dissemination in the lower respiratory tract,[8,9] with K. pneumoniae being responsible for 9.8%. In vivo dispersal of P. aeruginosa biofilm induced by enzymatic agents causes lethal septicemia in a mouse wound model.[17]

Methods

Results

Conclusion