Acinetobacter baumannii

Acinetobacter baumannii is a typically short, almost round, rod-shaped (coccobacillus) Gram-negative bacterium. It can be an opportunistic pathogen in humans, affecting people with compromised immune systems, and is becoming increasingly important as a hospital-derived (nosocomial) infection. It has also been isolated from environmental soil and water samples. Bacteria of this genus lack flagella, whip-like structures many bacteria use for locomotion, but exhibit twitching or swarming motility. This may be due to the activity of type IV pili, pole-like structures that can be extended and retracted. Motility in A. baumannii may also be due to the excretion of exopolysaccharide, creating a film of high-molecular-weight sugar chains behind the bacterium to move forward. Clinical microbiologists typically differentiate members of the Acinetobacter genus from other Moraxellaceae by performing an oxidase test, as Acinetobacter spp. are the only members of the Moraxellaceae to lack cytochrome c oxidases. A. baumannii is part of the ACB complex (A. baumannii, A. calcoaceticus, and Acinetobacter genomic species 13TU). Members of the ACB complex are difficult to determine the specific species, and comprise the most clinically relevant members of the genus. A. baumannii has also been identified as an ESKAPE pathogen (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species; a group of pathogens with a high rate of antibiotic resistance that are responsible for the a majority of nosocomial infections. Colloquially, A. baumannii is referred to as 'Iraqibacter' due to its seemingly sudden emergence in military treatment facilities during the Iraq War. It has continued to be an issue for veterans and soldiers who served in Iraq and Afghanistan. Multidrug-resistant A. baumannii has spread to civilian hospitals in part due to the transport of infected soldiers through multiple medical facilities.

Virulence factors and determinants

Many microbes, including A. baumannii, have several properties that allow them to be more successful as pathogens. These properties may be virulence factors such as toxins or toxin delivery systems which directly affect the host cell. They may also be virulence determinants, which are qualities contributing to a microbe's fitness and allow it to survive the host environment, but that do not affect the host directly. These characteristics are just some of the known factors which make A. baumannii effective as a pathogen:

AbaR resistance islands

Pathogenicity islands, relatively common genetic structures in bacterial pathogens, are composed of two or more adjacent genes that increase a pathogen's virulence. They may contain genes that encode toxins, coagulate blood, or, as in this case, allow the bacteria to resist antibiotics. AbaR-type resistance islands are typical of drug-resistant A. baumannii, and different variations may be present in a given strain. Each consists of a transposon backbone of about 16.3 Kb that facilitates horizontal gene transfer. Transposons allow portions of genetic material to be excised from one spot in the genome and integrate into another. This makes horizontal gene transfer of this and similar pathogenicity islands more likely because, when genetic material is taken up by a new bacterium, the transposons allow the pathogenicity island to integrate into the new microorganism's genome. In this case, it would grant the new microorganism the potential to resist certain antibiotics. AbaRs contain several genes for antibiotic resistance, all flanked by insertion sequences. These genes provide resistance to aminoglycosides, aminocyclitols, tetracycline, and chloramphenicol.

Beta-lactamase

A. baumannii has been shown to produce at least one beta-lactamase, which is an enzyme responsible for cleaving the four-atom lactam ring typical of beta-lactam antibiotics. Beta-lactam antibiotics are structurally related to penicillin, which inhibits synthesis of the bacterial cell wall. By cleaving the lactam ring, these antibiotics are rendered harmless to the bacteria. The beta-lactamase OXA-23 was found to be flanked by insertion sequences, suggesting it was acquired by horizontal gene transfer.

Biofilm formation

A. baumannii has been noted for its apparent ability to survive on artificial surfaces for an extended period of time, therefore allowing it to persist in the hospital environment. This is thought to be due to its ability to form biofilms. For many biofilm-forming bacteria, the process is mediated by flagella. However, for A. baumannii, this process seems to be mediated by pili. Further, disruption of the putative pili chaperone and usher genes csuC and csuE were shown to inhibit biofilm formation. The formation of biofilms has been shown to alter the metabolism of microorganisms within the biofilm, consequently reducing their sensitivity to antibiotics. This may be because less nutrients are available deeper within the biofilm. A slower metabolism can prevent the bacteria from taking up an antibiotic or performing a vital function fast enough for particular antibiotics to have an effect. They also provide a physical barrier against larger molecules and may prevent desiccation of the bacteria.

Capsule

Many virulent bacteria possess the ability to generate a protective capsule around each individual cell. This capsule, made of long chains of sugars, provides an extra physical barrier between antibiotics, antibodies, and complement. The association of increased virulence with presence of a capsule was classically demonstrated in Griffith's experiment. A gene cluster responsible for secretion of the polysaccharide capsule has been identified and shown to inhibit the antibiotic effect of complement when grown on ascites fluid. A decrease in killing associated with loss of capsule production was then demonstrated using a rat virulence model.

Efflux pumps

Efflux pumps are protein machines that use energy to pump antibiotics and other small molecules that get into the bacterial cytoplasm and the periplasmic space out of the cell. By constantly pumping antibiotics out of the cell, bacteria can increase the concentration of a given antibiotic required to kill them or inhibit their growth when the target of the antibiotic is inside the bacterium. A. baumannii is known to have two major efflux pumps which decrease its susceptibility to antimicrobials. The first, AdeB, has been shown to be responsible for aminoglycoside resistance. The second, AdeDE, is responsible for efflux of a wide range of substrates, including tetracycline, chloramphenicol, and various carbapenems.

OMPA

Adhesion can be a critical determinant of virulence for bacteria. The ability to attach to host cells allows bacteria to interact with them in various ways, whether by type III secretion system or simply by holding on against the prevailing movement of fluids. Outer membrane protein A has been shown to be involved in the adherence of A. baumannii to epithelial cells. This allows the bacteria to invade the cells through the zipper mechanism. The protein was also shown to localize to the mitochondria of epithelial cells and cause necrosis by stimulating the production of ROS.

Course of treatment for infection

Because most infections are now resistant to multiple drugs, it is necessary to determine what susceptibilities the particular strain has for treatment to be successful. Traditionally, infections were treated with imipenem or meropenem, but a steady rise in carbapenem-resistant A. baumannii has been noted. Consequently, treatment methods often fall back on polymixins, particularly colistin. Colistin is considered a drug of last resort because it often causes kidney damage among other side effects. Prevention methods in hospitals focus on increased hand-washing and more diligent sterilization procedures.

Occurrence in veterans injured in Iraq and Afghanistan

Soldiers in Iraq and Afghanistan are at risk for traumatic injury due to gunfire and improvised explosive devices. Previously, infection was thought to occur due to contamination with A. baumannii at the time of injury. Subsequent studies have shown, although A. baumannii may be infrequently isolated from the natural environment, the infection is more likely nosocomially acquired, likely due to the ability of A. baumannii to persist on artificial surfaces for extended periods, and the several facilities to which injured soldiers are exposed during the casualty-evacuation process. Injured soldiers are first taken to level-I facilities, where they are stabilized. Depending on the severity of the injury, the soldiers may then be transferred to a level-II facility, which consists of a forward surgical team, for additional stabilization. Depending on the logistics of the locality, the injured soldiers may transfer between these facilities several times before finally being taken to a major hospital within the combat zone (level III). Generally after 1â€"3 days, when the patients are stabilized, they are transferred by air to a regional facility (level IV) for additional treatment. For soldiers serving in Iraq or Afghanistan, this is typically Landstuhl Regional Medical Center in Germany. Finally, the injured soldiers are transferred to hospitals in their home country for rehabilitation and additional treatment. This repeated exposure to many different medical environments seems to be the reason A. baumannii infections have become increasingly common. Multidrug-resistant A. baumannii is a major factor in complicating the treatment and rehabilitation of injured soldiers, and has led to additional deaths.

Incidence of A. baumannii in hospitals

The importation of A. baumannii and subsequent presence in hospitals has been well documented. A. baumannii is usually introduced into a hospital by a colonized patient. Due to its ability to survive on artificial surfaces and resist desiccation, it can remain and possibly infect new patients for some time. A baumannii growth is suspected to be favored in hospital settings due to the constant use of antibiotics by patients in the hospital. In a study of European intensive care units in 2009, A. baumannii was found to be responsible for 19.1% of ventilator-associated pneumonia (VAP) cases.

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