Differential Role of the T6SS in Acinetobacter baumannii Virulence

Abstract

Gram-negative bacteria, such as Acinetobacter baumannii, are an increasing burden in hospitals worldwide with an alarming spread of multi-drug resistant (MDR) strains. Herein, we compared a type strain (ATCC17978), a non-clinical isolate (DSM30011) and MDR strains of A. baumannii implicated in hospital outbreaks (Ab242, Ab244 and Ab825), revealing distinct patterns of type VI secretion system (T6SS) functionality. The T6SS genomic locus is present and was actively transcribed in all of the above strains. However, only the A. baumannii DSM30011 strain was capable of killing Escherichia coli in a T6SS-dependent manner, unlike the clinical isolates, which failed to display an active T6SS in vitro. In addition, DSM30011 was able to outcompete ATCC17978 as well as Pseudomonas aeruginosa and Klebsiella pneumoniae, bacterial pathogens relevant in mixed nosocomial infections. Finally, we found that the T6SS of DSM30011 is required for host colonization of the model organism Galleria mellonella suggesting that this system could play an important role in A. baumannii virulence in a strain-specific manner.

Light Modulates Metabolic Pathways and Other Novel Physiological Traits in the Human Pathogen Acinetobacter baumannii

“…The T6SS is a class of macromolecular secretion machines that could be regarded as a potent weapon used by many Gramnegative bacteria to kill competitors (20). It has been shown that certain strains of A. baumannii produce a functional T6SS, which has been found to be implicated in virulence and host colonization in a strain-specific manner (21)(22)(23)(24).…”

Pathogenic Acinetobacter: from the Cell Surface to Infinity and Beyond

“…Notably, the main T6SS cluster does not contain vgrG genes, which are instead scattered throughout the genome. The VgrG proteins of Acinetobacter, which differ in number from strain to strain, do not seem to include effector domains (86,88). Instead, bioinformatic analyses suggest that the proteins are most likely to mediate the secretion of adjacently encoded toxic effectors, with cognate immunity proteins being encoded nearby (88).…”

“…The primary function of the T6SS in Acinetobacter seems to be to kill competing bacteria, and Acinetobacter spp. with active T6SSs are able to kill a wide variety of other bacteria, including other strains of the same species (64,(87)(88)(89).…”

“…T6SS activities vary widely in different strains and species of Acinetobacter, with some strains showing robust T6SSs and bacterial killing and others seeming to have inactive systems under laboratory conditions (64,(86)(87)(88). However, the available data suggest that strains with T6SSs invariably express the main protein Hcp to at least some level, with variations in whether the protein is secreted (thus determining whether the system is active) (64,86,88). In A. baumannii ATCC 19606, Hcp is constitutively secreted in wild-type cells but is lost in mutants lacking lipid A, potentially due to membrane disruptions (85).…”

“…It should be noted that several recent multidrugresistant (MDR) A. baumannii strains seem to have permanently inactivated their T6SSs through chromosomal gene loss; it has been suggested that this may be a result of the antibiotic pressure being great enough to make it evolutionarily advantageous to completely lose the T6SS, rather than maintaining it in an inactive state (93). Although there are limited data, there appears to be a link between antibiotic resistance and T6SS status in Acinetobacter; strains that are multidrug resistant express but do not secrete Hcp, while those that are not multidrug resistant are more likely to have an active T6SS (64,86,88).…”