Importance of flagella in acute and chronic Pseudomonas aeruginosa infections

Abstract

Summary Pseudomonas aeruginosa is an environmental microorganism and a causative agent of diverse acute and chronic, biofilm‐associated infections. Advancing research‐based knowledge on its adaptation to conditions within the human host is bound to reveal novel strategies and targets for therapeutic intervention. Here, we investigated the traits that P. aeruginosa PA14 as well as a virulence attenuated ΔlasR mutant need to survive in selected murine infection models. Experimentally, the genetic programs that the bacteria use to adapt to biofilm‐associated versus acute infections were dissected by passaging transposon mutant libraries through mouse lungs (acute) or mouse tumours (biofilm‐infection). Adaptive metabolic changes of P. aeruginosa were generally required during both infection processes. Counter‐selection against flagella expression was observed during acute lung infections. Obviously, avoidance of flagella‐mediated activation of host immunity is advantageous for the wildtype bacteria. For the ΔlasR mutant, loss of flagella did not confer a selective advantage. Apparently, other pathogenesis mechanisms are active in this virulence attenuated strain. In contrast, the infective process of P. aeruginosa in the chronic biofilm model apparently required expression of flagellin. Together, our findings imply that the host immune reactions against the infectious agent are very decisive for acuteness and duration of the infectious disease. They direct disease outcome.

An Organ System-Based Synopsis ofPseudomonas aeruginosaVirulence

“…On the other hand, using Tn-seq with a transposon mutant library of strain PA14 in an acute pneumonia mice model, Lorenz et al . (2019) found that the flagellum and T4P were not required to cause infections [ 130 ]. In fact, mutants with transposon insertions in the pili and flagellar biogenesis operons ( pil, flg and fli operons) were enriched (positively selected) in this infection model.…”

Cwp22, a novel peptidoglycan cross‐linking enzyme, plays pleiotropic roles in Clostridioides difficile

“…These toxins can disrupt the actin cytoskeleton of intestinal epithelial cells through glucosylation of the Rho family of GTPases to induce mucosal inflammation and the symptoms associated with CDI (Peniche et al, 2013). Other important virulence traits that impact host infection and colonization include: (i) cell wall proteins (CWPs) (Biazzo et al, 2013); (ii) tissue degradative proteases (Seddon et al, 1990;Seddon and Borriello, 1992;Borriello, 1995); (iii) flagella and fimbriae (Edwards et al, 2000;Stevenson et al, 2015;Lorenz et al, 2019).…”

Pseudomonas syringaedual‐function protein Lon switches between virulence and metabolism by acting as bothDNA‐binding transcriptional regulator and protease in different environments

“…For example, Lon degrades FlhD in P. mirabilis (Rogers et al, 2016) and SwrA (a master activator of swarming motility) in B. subtilis (Mukherjee et al, 2015). In the ΔlasR transposon mutant library, lon mutants are negatively enriched during acute lung infection but not in biofilm-associated infection (Lorenz et al, 2019). In P. aeruginosa, Lon also degrades HigA, which regulates mvfR that encodes the master regulator for biofilm and motility (Guo et al, 2019).…”