A Cyclic-di-GMP signalling network regulates biofilm formation and surface associated motility of Acinetobacter baumannii 17978

Abstract

Acinetobacter baumannii has emerged as an increasing multidrug-resistant threat in hospitals and a common opportunistic nosocomial pathogen worldwide. However, molecular details of the pathogenesis and physiology of this bacterium largely remain to be elucidated. Here we identify and characterize the c-di-GMP signalling network and assess its role in biofilm formation and surface associated motility. Bioinformatic analysis revealed eleven candidate genes for c-di-GMP metabolizing proteins (GGDEF/EAL domain proteins) in the genome of A. baumannii strain 17978. Enzymatic activity of the encoded proteins was assessed by molecular cloning and expression in the model organisms Salmonella typhimurium and Vibrio cholerae. Ten of the eleven GGDEF/EAL proteins altered the rdar morphotype of S. typhimurium and the rugose morphotype of V. cholerae. The over expression of three GGDEF proteins exerted a pronounced effect on colony formation of A. baumannii on congo Red agar plates. Distinct panels of GGDEF/EAL proteins were found to alter biofilm formation and surface associated motility of A. baumannii upon over expression. The GGDEF protein A1S_3296 appeared as a major diguanylate cyclase regulating macro-colony formation, biofilm formation and the surface associated motility. AIS_3296 promotes Csu pili mediated biofilm formation. We conclude that a functional c-di-GMP signalling network in A. baumannii regulates biofilm formation and surface associated motility of this increasingly important opportunistic bacterial pathogen.

Analysis of virulence phenotypes and antibiotic resistance in clinical strains of Acinetobacter baumannii isolated in Nashville, Tennessee

“…Analysis of biofilm formation also revealed that isolates derived from patient blood samples formed significantly more biofilm than isolates from sputum or bronchial wash, or isolates from wound samples. Both biofilm and motility phenotypes have been shown to vary widely across clinically isolated strains of A. baumannii [ 23 ] and both processes have both been shown to be regulated by overlapping signaling networks in this pathogen [ 24 , 25 ]. Although biofilm and motility phenotypes varied widely across strains in our study as well, we observed an inverse relationship between motility and biofilm formation in the 17 clinical isolates examined.…”

Insights into Acinetobacter baumannii: A Review of Microbiological, Virulence, and Resistance Traits in a Threatening Nosocomial Pathogen

“…In addition to twitching motility, some isolates of A. baumannii move on living and non-living surfaces without relying on flagella by another mode of motility called surface-associated motility [97]. This type of motility also requires type IV pili, quorum sensing, lipo-oligosaccahride production, and 1,3-diaminopropane, which mediates signaling needed for impacting surface-associated motility by quorum sensing [90].…”

Mechanisms Protecting Acinetobacter baumannii against Multiple Stresses Triggered by the Host Immune Response, Antibiotics and Outside-Host Environment

“…Most c-di-GMP-dependent signalling pathways regulate the bacteria ability to interact with abiotic surfaces or with other bacterial and eukaryotic cells. Eleven genes for GGDEF/EAL proteins in the genome of the A. baumannii 17 , 978 strain were identified, and most of the predicted proteins were enzymatically active [ 118 ]. It was demonstrated that distinct panels of these enzymes promote biofilm formation, macro-colony growth, and surface-associated motility [ 118 ].…”

“…cAMP inhibits pellicle formation [ 104 ]. The synthesis of Csu pili depends on cyclic di-GMP (c-di-GMP) [ 118 ] and the BfmRS and GacSA systems [ 48 , 119 , 120 ]. The hybrid two-component regulator CheA/Y controls the expression of Csu pili and acinetin-505 via QS [ 106 , 121 ].…”