Acinetobacter baumannii virulence determinants involved in biofilm growth and adherence to host epithelial cells

KEYWORDS:

• abiotic surfaces
• Acinetobacter baumannii
• biofilm growth
• epithelial cells adherence
• type I pilus

This article refers to:

Analysis of the role of the LH92_11085 gene of a biofilm hyper-producing Acinetobacter baumannii strain on biofilm formation and attachment to eukaryotic cells

Acinetobacter baumannii is a gram-negative coccobacillus, which emerged as important global pathogens during the past 20 years, exhibiting resistance to the majority of available antibiotics and disinfectants.¹ A. baumannii causes large and persistent outbreaks among hospitalized patients and is able to contaminate biotic and abiotic surfaces, such as vascular and urinary catheters, cerebrospinal fluid shunts, and endotracheal intubation devices.¹ A. baumannii strains responsible for epidemics show elevated resistance to desiccation, high biofilm-forming capacity on abiotic surfaces and adherence to host epithelial cells, virulence-related features which might have favored the spread and persistence in the hospital environment.^2,3 Biofilm formation in A. baumannii has been shown to be positively correlated with the expression of chaperone–usher type I pili assembly system,^4,5 the outer membrane protein OmpA,⁶ the extracellular polysaccharide poly-β-(1,6)-N-acetyl glucosamine (PNAG),⁷ a homolog of the staphylococcal biofilm-associated protein (BAP),^8,9 and two recently identified BAP-like proteins (BLP)-1 and (BLP)-2.¹⁰ Also, A. baumannii is able to form a tight biofilm structure at air-liquid interface, which is generally referred as pellicle and is associated with the presence of poly-Nacetylglucosamine (PNAG) polysaccharide and csuA/B usher protein of pili assembly system.¹¹ Moreover, genes involved in motility, iron acquisition, quorum sensing and those encoding efflux system components such as RND efflux pump AdeT are over-expressed during biofilm growth of A. baumannii ATCC 17978 cells; disruption or deletion of these genes causes a significant decrease in biofilm formation ability in the corresponding mutant strains.¹² Virulence determinants involved in biofilm growth, including OmpA, BAP, BLP-1 and BLP-2,^6,10,13 regulate adherence/invasion of A. baumannii to host epithelial cells, thus explaining the correlation between biofilm formation and adherence to host epithelial cells found in epidemic A. baumannii isolates.^2,3

In this issue of Virulence, Álvarez-Fraga and coworkers¹⁴ identify a gene coding for a putative pilus rod, which is responsible for mature biofilm formation and adherence to eukaryotic cells of biofilm hyper-producing A. baumannii MAR002 strain.¹⁵ Based on previous studies demonstrating the role of pili proteins on biofilm formation and adhesion to abiotic surfaces in A. baumannii,^4,5,11,12 authors have selected the LHp2_11085 gene of MAR002 strain among predicted genes potentially involved in pili formation and over- expressed in biofilm-associated cells compared to exponential planktonic cells. The gene encodes a putative protein homologous to the major type I pilus subunit fimA of E. coli¹⁶ and is included into an operon of 4 genes. The inactivation of LHp2_11085 gene results in reduced biofilm formation on plastic surfaces and impairment in the attachment of bacteria to A549 human alveolar epithelial cells. Both phenotypes are reverted by complementation of the knock-out mutant with the parental allele. Also, inactivation of LHp2_11085 gene inhibits the formation of longer type of pili, a pili-like structure found in biofilm hyper-producing A. baumannii MAR002 cells but not in biofilm scarce producing A. baumannii ATCC 17978 cells. Moreover, the lack of LHp2_11085 gene impairs the ability of A. baumannii MAR002 to reduce the viability of A549 cells. Based on their findings, the authors conclude that LHp2_11085 gene is required for the development of mature biofilm structure on abiotic surfaces, attachment of bacteria to human epithelial cells and ability to cause eukaryotic cell death. They speculate that LHp2_11085 gene plays an important role during A. baumannii infection and represents a potential target to impair host-pathogen interactions. In further support of this, it has been recently demonstrated that surface exposed proteins involved in biofilm formation are good vaccine candidates against A. baumannii sepsis infection.¹⁷ Following on from this, it would be desirable to determine the pathogenic role of LHp2_11085 gene and its potential use as target in an in vivo model of infection such as the larvae of the wax moth Galleria mellonella, which allows to study A. baumannii pathogenesis and therapeutics.¹⁸ These studies are required to validate the use of the protein encoded by the LHp2_11085 gene of MAR002 strain as target for antimicrobial strategies against A. baumannii.

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.