Multidrug resistant Acinetobacter baumannii: A study on its pathogenesis and therapeutics

Abstract

The overuse of antibiotics has led to the global dissemination of Acinetobacter baumannii, an increasingly challenging nosocomial pathogen. This review explores the medical significance along with the diverse resistance ability of A. baumannii. Intensive care units (ICUs) serve as a breeding ground for A. baumannii, as these settings harbour vulnerable patients and facilitate the spread of opportunistic microorganisms. A. baumannii belongs to the ESKAPE group of bacterial pathogens that are major contributors to antibiotic-resistant infections. The pathogenic nature of A. baumannii is particularly evident in seriously ill patients, causing pneumonia, wound infections, and other healthcare-associated infections. Historically considered benign, A. baumannii is a global threat due to its propensity for rapid acquisition of multidrug resistance phenotypes. The genus Acinetobacter was formally recognized in 1968 following a comprehensive survey by Baumann et al., highlighting the relationship between previously identified species and consolidating them under the name Acinetobacter. A. baumannii is characterized by its Gram-negative nature, dependence on oxygen, positive catalase activity, lack of oxidase activity, inability to ferment sugars, and non-motility. The DNA G+C content of Acinetobacter species falls within a specific range. For diagnostic purposes, A. baumannii can be cultured on specific agar media, producing distinct colonies. The genus Acinetobacter comprises numerous species those are associated with bloodstream infections with high mortality rates. Therefore, A. baumannii poses a significant challenge to global healthcare due to its multidrug resistance and ability to cause various infections. A comprehensive understanding of the mechanisms underlying its resistance acquisition and pathogenicity is essential for combating this healthcare-associated pathogen effectively.

Keywords: Acinetobacter baumannii; Hospital acquired pneumonia; Multidrug resistant organism; Pathogenesis; Urinary tract infection.

Graphical abstract

Fig 1

Schematic timeline showing the emergence of Acinetobacter Baumannii.

Fig 2

Schematic diagram of different diseases caused by A. baumannii. Such as the bacterial infection of meninges known as meningitis. The most affected is nosocomial pathogenic pneumonia in patients admitted to hospitals such as HAP (Hospital Acquired Pneumonia) and VAP (Ventilator-associated pneumonia). Septicemia or the bloodstream infection, urinary tract infection, and surgical site infection for its MDR nature.

Fig 3

Steps leading toward biofilm formation. First, the A. baumannii attaches to the surface and a colony is formed. Individual cells communicate with each other via quorum sensing, releasing molecules such as autoinducers like AHL (Acetylhomoserin lactose). Cells aggregate and adhere to each other via exopolysaccharides. Proteins on the bacterial surface (Bap) help in the maturation of the biofilm. Finally, the biofilm helps in evading immune cells, resistance to antibiotics, and protects against environmental stresses.

Fig 4

Adhesion and recognition of A. baumannii by host neutrophil. A. baumannii binds with neutrophil via IL-8 receptor interaction. TLRs help in the recognition of A. baumannii cells through their OMPs, lipoproteins, peptidoglycans (TLR4), and lipoteichoic acid (TLR2). IgG and complement protein binding with neutrophil and TLR activation via binding of A. baumannii in IL-8 receptor mediated fashion activates CD14 which in turn activates NF-κβ transcription factor. It results in the secretion of pro-inflammatory cytokines (TNF-α, IFNγ, IL-1,8 and 10). Neutrophil surface receptors CD11a and CD11b reduce the adhesion of A. baumannii cells.

Fig 5

Mechanism of antibiotics resistance in A. baumannii. A. β-lactams (penicillin, amoxicillin, etc.) when entering into A. baumannii cells, β-lactamase like Ambler class A and B hydrolyze the antibiotics. Class C cephalosporinase hydrolyzes cephalosporins and class D distorts oxacillin. B. Tetracyclines are actively pumped outside of the cell by efflux pumps upon entry inside the bacterial cells. Nodulation division family type pumps (RND pumps) also participate in the same function. C. Mutation of enzymes such as DNA gyrase at the Ser83 and Gly81 prevents the binding of the fluoroquinolones to the DNA gyrase-DNA complex. D. Different 16S rRNA (rmtA, armA, rmtB) alter the 30S ribosome subunit binding sites for aminoglycosides.