Deciphering the virulence factors, regulation, and immune response to Acinetobacter baumannii infection

Shadan, Afreen; Pathak, Avik; Ying, Ma; Pathania, Ranjana; Singh, Raju

doi:10.3389/fcimb.2023.1053968

Cited by 18 publications

(22 citation statements)

References 232 publications

(237 reference statements)

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“…Through a wide range of pan-genomic studies, it has been recognized that A. baumannii is an open pan-genomic bacterial pathogen; hence, A. baumannii encompasses a variety of virulence factors with different functions and activities. Because of the importance of these virulence factors, Table 1 shows a complete package of the identified virulence factors together with the related genes [ 3 , 68 , 69 ].…”

Section: Virulencementioning

confidence: 99%

“…CPS is known as the main virulence factor arming A. baumannii stains. This structure acts as a superficial multifunctional virulence factor that pathogenic bacteria like A. baumannii use to survive in unfavorable environmental conditions, such as the presence of antimicrobials, human host cell immune defense mechanisms and prolonged desiccation ( Table 2 ) [ 68 , 71 , 72 ]. The omission of CPS expression in CPS-producing A. baumannii strains may significantly affect bacterial virulency and pathogenesis.…”

Section: Virulencementioning

confidence: 99%

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Pan-Genome Plasticity and Virulence Factors: A Natural Treasure Trove for Acinetobacter baumannii

Karampatakis,

Tsergouli,

Behzadi

2024

Antibiotics

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Acinetobacter baumannii is a Gram-negative pathogen responsible for a variety of community- and hospital-acquired infections. It is recognized as a life-threatening pathogen among hospitalized individuals and, in particular, immunocompromised patients in many countries. A. baumannii, as a member of the ESKAPE group, encompasses high genomic plasticity and simultaneously is predisposed to receive and exchange the mobile genetic elements (MGEs) through horizontal genetic transfer (HGT). Indeed, A. baumannii is a treasure trove that contains a high number of virulence factors. In accordance with these unique pathogenic characteristics of A. baumannii, the authors aim to discuss the natural treasure trove of pan-genome and virulence factors pertaining to this bacterial monster and try to highlight the reasons why this bacterium is a great concern in the global public health system.

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Section: Virulencementioning

confidence: 99%

Section: Virulencementioning

confidence: 99%

Pan-Genome Plasticity and Virulence Factors: A Natural Treasure Trove for Acinetobacter baumannii

Karampatakis,

Tsergouli,

Behzadi

2024

Antibiotics

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“…Of note, A. baumannii benefits from virulence factors such as outer membrane proteins (OMPs), metal ion acquisition systems, lipopolysaccahrides (LPS), efflux pumps, empowering it to survive harsh environments (e.g. host immune system, hospital environments) and resist antibiotics (15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Several studies have demonstrated that mAbs targeting these virulence factors could provide protection against infections caused by multidrug resistant (MDR) or extensively drug resistant (XDR) A. baumannii in animal models (15,(25)(26)(27)(28).…”

Section: Introductionmentioning

confidence: 99%

Two novel single-chain variable fragments exert bactericidal activity against Acinetobacter baumannii through destabilization of the outer membrane

Rahimi-Jamnani

2024

Preprint

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Acinetobacter baumannii is notorious for its high levels of resistance and the development of clinically-effective antimicrobial agents seems to be an urgent medical challenge. Bactericidal single-chain variable fragments (scFvs) are novel antibacterial agents capable of inhibiting the growth of pathogens (e.g. Staphylococcus aureus, Pseudomonas aeruginosa, A. baumannii) independently of the host immune system. We previously found that two fully human scFvs, EB211 and EB279, showed direct growth inhibition against A. baumannii strains in vitro and demonstrated therapeutic effectiveness in immunocompromised mice with pneumonia caused by an extensively drug-resistant A. baumannii strain. In the current study, the antibacterial activity of EB211 and EB279 against A. baumannii, Klebsiella pneumonia, and P. aeruginosa strains was appraised in the presence of a high concentration of magnesium (Mg2+; 20 mM) to find the bactericidal mechanism of these two scFvs. Furthermore, epitope mapping was performed to identify A. baumanniiproteins that might be bound by EB211 and EB279. It was found that EB211 and EB279, similar to colistin sulfate, lost their activity in the presence of Mg2+. Indeed, both EB211 and EB279 exerted their growth inhibitory activity through displacing Mg2+ and interrupting the integrity of the outer membrane. Taken together, EB211 and EB279 by disruption of the outer membrane A. baumannii elicit their main direct growth inhibitory activity against A. baumannii without the need for immune cells or complements.

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“…The virulence of A. baumannii is multifactorial, determined by the combination of multiple factors such as efflux pumps (adeRS), quorum sensing (aba), siderophores (bar, bas, bau), biofilm (bap), secretion systems (pil, TXSS), and one of the most important factors, the capsule [10].…”

Section: Introductionmentioning

confidence: 99%

Outbreak of High-risk XDR CRAB of International Clone 2 (IC2) in Rio Janeiro, Brazil

Morgado

Fonseca

Freitas

et al. 2023

Preprint

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The high-risk clones of Acinetobacter baumannii, called international clones (ICs), span several ICs, IC1 to IC7 being the most reported. Among them, IC2 represents the main lineage causing outbreaks worldwide. IC2 presents a great diversity of sub-lineages with different sequence types (ST). Despite successful global spread, the occurrence of IC2 is rarely reported in Latin America, including Brazil. Here, through genomic analysis, we investigated 16 IC2/ST2 strains obtained from a clinical setting in Brazil (2022). These strains represented carbapenem-resistant A. baumannii (CRAB) with an extensively drug-resistant (XDR) profile, with most showing some resistance to tigecycline. Overall, these strains showed susceptibility only to polymyxins, thus leading to restricted therapeutic choices. Based on in silico analysis, the relationship between Brazilian CRAB genomes and IC2/ST2 genomes circulating in the world, particularly in South America, was established. The Brazilian IC2 strains belonged to three discrete and distinct sub-lineages, being more associated with IC2/ST2 genomes from countries in Europe, North America and Asia, suggesting their epidemiological link. These Brazilian strains were characterized by the co-presence of blaOXA-23 and blaOXA-66, in addition to the genes APH(6), APH(3"), ANT(3"), AAC(6'), armA, and the efflux pumps adeABC and adeIJK, associated with the XDR/CRAB phenotype. Furthermore, the three sub-lineages presented three distinct capsules, KL7, KL9 and KL56, the latter not yet associated with IC2 genomes. A large set of virulence genes was also identified in the genomes: adeFGH/efflux pump, the siderophores barAB, basABCDFGHIJ and bauBCDEF, lpxABCDLM/capsule, tssABCDEFGIKLM/T6SS, pgaABCD/biofilm.

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Deciphering the virulence factors, regulation, and immune response to Acinetobacter baumannii infection

Cited by 18 publications

References 232 publications

Pan-Genome Plasticity and Virulence Factors: A Natural Treasure Trove for Acinetobacter baumannii

Pan-Genome Plasticity and Virulence Factors: A Natural Treasure Trove for Acinetobacter baumannii

Two novel single-chain variable fragments exert bactericidal activity against Acinetobacter baumannii through destabilization of the outer membrane

Outbreak of High-risk XDR CRAB of International Clone 2 (IC2) in Rio Janeiro, Brazil

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