Abstract
Currently, Acinetobacter baumannii is considered as one of the most important infectious agents causing hospital acquired infections worldwide. It has been observed that many clinically important pathogens express contact-dependent growth inhibition (CDI) phenomenon, which modulates cell–cell and cell–environment interactions, potentially allowing bacteria to adapt to ever-changing conditions. Mainly, these systems are used for the inhibition of the growth of genetically different individuals within the same species. In this work, by performing cell competition assays with three genotypically different (as determined by pulse-field gel electrophoresis) clinical A. baumannii isolates II-c, II-a, and II-a1, we show that A. baumannii capsule is the main feature protecting from CDI-mediated inhibition. We also observed that for one clinical isolate, the two-component BfmRS system, contributed to the resistance against CDI-mediated inhibition. Moreover, we were able to demonstrate, that the effector protein CdiA is released into the growth media and exhibits its inhibitory activity without the requirement of a cell–cell contact. Lastly, by evaluating the remaining number of the cells pre-mixed with the CdiA and performing live/dead assay, we demonstrate that purified CdiA protein causes a rapid cell growth arrest. Our results indicate, that capsule efficiently protects A. baumannii from a CDI-mediated inhibition by a clinical A. baumannii V15 strain, which is able to secrete CdiA effector into the growth media and cause target cell growth arrest without a cell–cell contact.
Highlights
Acinetobacter baumannii is a Gram-negative coccobacilli, that has recently emerged as an important nosocomial pathogen (Peleg et al, 2008)
We identified that the two-component system BfmRS negatively regulates contact-dependent growth inhibition (CDI) system in A. baumannii V15 clinical strain
We observed that capsule formation is essential for A. baumannii to be able to resist CDI-mediated inhibition
Summary
Acinetobacter baumannii is a Gram-negative coccobacilli, that has recently emerged as an important nosocomial pathogen (Peleg et al, 2008). The success of A. baumannii comes from the ability to display multi-drug resistance profile and persist in the surrounding environment (Harding et al, 2018). Carbapenem-resistant strains are classified as the priority 1 pathogens by World Health Organization, indicating critical importance for the research and development of a new antibacterial strategies against A. baumannii (Tacconelli et al, 2018). One of the main mechanisms that allows A. baumannii to persist in the Capsule Mediated Protection From CDI environment is through the use of various secretion systems (Weber et al, 2017; Harding et al, 2018). TPS systems have been shown to perform various functions such as secretion of virulence factors, adhesion, micro-nutrient uptake, and contact-dependent growth inhibition (CDI) within closely related strains (Willett et al, 2015b; Guérin et al, 2017)
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