Identification of a Contact-Dependent Growth Inhibition (CDI) System That Reduces Biofilm Formation and Host Cell Adhesion of Acinetobacter baumannii DSM30011 Strain

Abstract

Acinetobacter baumannii is a multidrug-resistant nosocomial opportunistic pathogen that is becoming a major health threat worldwide. In this study, we have focused on the A. baumannii DSM30011 strain, an environmental isolate that retains many virulence-associated traits. We found that its genome contains two loci encoding for contact-dependent growth inhibition (CDI) systems. These systems serve to kill or inhibit the growth of non-sibling bacteria by delivering toxins into the cytoplasm of target cells, thereby conferring the host strain a significant competitive advantage. We show that one of the two toxins functions as a DNA-damaging enzyme, capable of inducing DNA double-stranded breaks to the chromosome of Escherichia coli strain. The second toxin has unknown catalytic activity but stops the growth of E. coli without bactericidal effect. In our conditions, only one of the CDI systems was highly expressed in the A. baumannii DSM30011 strain and was found to mediate interbacterial competition. Surprisingly, the absence of this CDI system promotes adhesion of A. baumannii DSM30011 to both abiotic and biotic surfaces, a phenotype that differs from previously described CDI systems. Our results suggest that a specific regulation mediated by this A. baumannii DSM30011 CDI system may result in changes in bacterial physiology that repress host cell adhesion and biofilm formation.

Acinetobacter baumannii NCIMB8209: a Rare Environmental Strain Displaying Extensive Insertion Sequence-Mediated Genome Remodeling Resulting in the Loss of Exposed Cell Structures and Defensive Mechanisms

“…Searching for other competition mechanisms such as the two-partner systems (Tps) already identified in strain DSM30011 ( Fig. 2 ) related to contact-dependent inhibition (CDI) ( 57 ) also resulted in negative results. These observations led us to hypothesize that the ability of strain NCIMB8209 to outcompete other bacteria was severely compromised.…”

Structural insight into toxin secretion by contact-dependent growth inhibition transporters

“…An increasing number of studies have reported multifunctional roles for CdiA proteins, apparently independent of toxin activity. CdiA promotes adhesion on epithelial cells in A. baumannii, plays a major role in intracellular survival and intracellular escape in Neisseria meningitidis , increases the virulence of Pseudomonas aeruginosa in infection models, and controls biofilm establishment in human pathogens ( Melvin et al, 2017 ; Mercy et al, 2016 ; Pérez et al, 2016 ; Roussin et al, 2019 ; Talà et al, 2008 ). Both CDI systems investigated in our study have been shown to be constitutively active, and a secretome analysis of Acinetobacter spp.…”

Contact-Dependent Growth Inhibition in Bacteria: Do Not Get Too Close!

“…(Burkholderia thailandensis, Burkholderia dolosa) [52][53][54][55][56][57][58][59], N. meningitidis [60], P. aeruginosa [61][62][63][64], and Acinetobacter spp. (A. baumannii, Acinetobacter baylyi) [65][66][67][68] (Table 1), while proteins similar to CdiA-CT toxin were identified also in Gram-positive species including Bacillus, Listeria, Clostridium, and Streptococcus [31]. Such proteins derived from Bacillus subtilis or Bacillus cereus and expressed in E. coli showed RNase activity and suppressed the growth of wild E. coli strains [31].…”