Acinetobacter baumannii: The Emergence of a Dangerous Multidrug-Resistant Pathogen

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By: Kerri-Lynn Conrad

Figure 1. A colored SEM depiction of Acinetobacter baumannii, an emerging multidrug-resistant pathogen that causes opportunistic infections associated with high mortality rates.

Introduction

Figure 2. SEM depiction of a cluster of gram-negative, non-motile, rod bacteria Acinetobacter baumannii.

Genome Structure

Figure 3. The genome of Acinetobacter baumannii consists of 3,976,746 base pairs. Several pathogenicity islands were identified in the genome through sequence homology comparisons.

The genome of Acinetobacter baumannii contains 3,976,746 base pairs and is composed of 3830 open reading frames. Approximately 17.2% of the open-reading frames are located within putative alien islands, highlighting Acinetobacter baumannii’s remarkable ability to incorporate foreign DNA into its genome (1).

Acinetobacter baumannii has several genes that permit it to pick up foreign DNA from its environment, as well as other microbes. These genes include PilQ, ComE, and PilF, commonly found in gram-negative bacteria, as well as closely related species Acinetobacter baylyi. Interestingly, the genome of Acinetobacter baumannii lacks a gene for ComP, a gene for a membrane transporter important for foreign DNA uptake in many species. Nonetheless, the ComEA gene of A. baumannii codes for a transmembrane protein that can bind foreign DNA in the environment and transport it to the internal environment of the cell where it can be incorporated into the genome. One study has suggested that the ComEA gene or possibly even the type IV pilus of A. baumannii allow it to effectively obtain foreign DNA from the environment, thus eliminating the need for the ComP gene found in many other species (1).

Closely tied to A. baumanniii’s ability to obtain foreign DNA for incorporation into its own genome are the putative alien islands (pAs) that permit the pathogenicity of A. baumanniii, distinguishing it from other Acinetobacter species. pAs obtained from the environment or from other species can possess a variety of functions. Nevertheless, many of the pAs that remain preserved in the A. baumanniigenome are responsible for pathogenic and virulence factors, and are deemed PAIs. Of the approximately 28 pAs in the A. baumannii genome, 12 share significant sequence identity with virulence genes in other species of bacteria. The largest of these PAIs is a 133,740 base pair island containing several transposons, integrases, and eight genes with significant sequence homology to Legionella/Coxiella Type IV virulence/secretion apparatus (1). Seven of the twelve PAIs contain genes that encode proteins or efflux pumps that confer drug resistance to A. baumanniii, although many strains of A. baumanniidevelop additional drug resistance genes through the evolutionary pressures of treatment with pharmaceuticals (1).

In addition to the virulence-conferring genes of the A. baumannii PAIs, the pAs obtained by the bacterium from the outside environment include genes for heavy metal resistance, iron metabolism, quorum sensing capabilities, lipid metabolism, amino acid uptake, and genes for the breakdown of xenobiotics (1).

Of paramount importance to the pathogenic potential of A. baumannii are the plethora of antibiotic resistance genes contained within its genome. The AYE strain of A. baumannii has a 86,190 base pair PAI inserted into its genome that contains 45 of its 52 drug resistance genes (2). Similarly, a more recent isolate, the ATCC17978 strain of A. baumannii contains a 13,277 base pair PAI that contains 74 drug resistance genes, 32 efflux pumps, 11 genes related to drug/metabolite transporters (DMTs), as well as 26 genes encoding resistance to a variety of heavy metals, including copper, cadmium, zinc, and arsenic (1). The drug resistance genes on the PAI of this strain confer resistance to several classes of antibiotics, including β -lactams, aminoglycosides, fluoroquinolones, chloramphenicol, tetracycline, and rifampin (2). Genomic comparisons of the AYE and ATCC17978 A. baumannii strains suggest that the ATCC17978 strain has disposed of some of the drug resistance genes observed in the AYE strain in order to evolve a potent drug resistance cassette observed in its genomically inserted PAI (1). It is clear from these genomic analyses that the ability to obtain foreign DNA from environmental sources has proven immensely important in the development of A. baumannii pathogenesis. It is likely that this pathogen will continue to optimize its virulent potential through the attainment, integration, and use of foreign genes.

Cell Structure

Figure 4. Acinetobacter baumannii membrane transporter PilQ allows initial entry of foreign DNA into the cell. Foreign DNA is then bound by protein ComE and is directed to cytoplasmic membrane transporter ComA.

Epidemiology

Figure 5. Several regions around the world are attempting to deal with outbreaks of Acinetobacter baumannii infection. Although Acinetobacter baumannii has been a problem in hospitals for many years, the pathogen started to receive attention after the rise in infections among soldiers serving in Iraq and Afghanistan.

Pathology

Figure 6. Acinetobacter baumannii can be found in the natural microbial flora of the human skin. However, some pathogenic strains can infect the human respiratory tract, open wounds, or the bloodstream. Acinetobacter baumannii's resistance to many antibiotics and diverse metabolism allows it to subsist in various environments.

Multidrug-Resistance

Figure 7. In a study conducted in four community hospitals on Acinetobacter baumannii infections in patients over the age of 60, the pathogen gained resistance to all 8 antibiotic classes tested in only five years.

Implications for Hospitals

Figure 8. Acinetobacter baumannii infections among immune compromised patients is a major problem in hospitals. Susceptible patients often obtain the infection from hospital equipment, staff members, or other patients.

Outbreak in United States Military Treatment Facilities

Figure 9. An American soldier at a military field hospital battling Acinetobacter baumannii that infected an open wound.

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Edited by Kerri-Lynn Conrad, student of Joan Slonczewski for BIOL 238 Microbiology, 2011, Kenyon College.