A Porcine Wound Model of<i>Acinetobacter baumannii</i>Infection

Zurawski, Daniel V.; Black, Chad; Alamneh, Yonas; Biggemann, Lionel; Banerjee, Jaideep; Thompson, Mitchell G.; Wise, Matthew C.; Honnold, Cary L.; Kim, Robert K.; Paranavitana, Chrysanthi; Shearer, Jonathan P.; Tyner, Stuart D.; Demons, Samandra

doi:10.1089/wound.2018.0786

Cited by 20 publications

(25 citation statements)

References 65 publications

(67 reference statements)

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“…Bacteria are the main cause of the 14 million outpatient and 850,000 inpatient skin and soft-tissue infections (SSTIs) each year [ 33 ]. Members of the ESKAPE ( E nterococcus faecium , S taphylococcus aureus , K lebsiella pneumoniae , A cinetobacter baumannii , P seudomonas aeruginosa , and E nterobacter species) family make up the bulk of SSTIs, with A. baumannii a leading cause of SSTIs that occur within a military environment [ 4 , 31 , 34 ].…”

Section: Introduction To a Baumanniimentioning

confidence: 99%

Recent Advances in the Pursuit of an Effective Acinetobacter baumannii Vaccine

2020

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Acinetobacter baumannii has been a major cause of nosocomial infections for decades. The absence of an available vaccine coupled with emerging multidrug resistance has prevented the medical community from effectively controlling this human pathogen. Furthermore, the ongoing pandemic caused by SARS-CoV-2 has increased the risk of hospitalized patients developing ventilator-associated pneumonia caused by bacterial opportunists including A. baumannii. The shortage of antibiotics in the development pipeline prompted the World Health Organization to designate A. baumannii a top priority for the development of new medical countermeasures, such as a vaccine. There are a number of important considerations associated with the development of an A. baumannii vaccine, including strain characteristics, diverse disease manifestations, and target population. In the past decade, research efforts have revealed a number of promising new immunization strategies that could culminate in a safe and protective vaccine against A. baumannii. In this review, we highlight the recent progress in the development of A. baumannii vaccines, discuss potential challenges, and propose future directions to achieve an effective intervention against this human pathogen.

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Section: Introduction To a Baumanniimentioning

confidence: 99%

Recent Advances in the Pursuit of an Effective Acinetobacter baumannii Vaccine

2020

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“…Biofilm formation is an important component of the A. baumannii lifecycle; the bacterium is known to create biofilms on both biotic and abiotic surfaces, which aides in fomite-based transmission and in virulence (Longo et al, 2014;Zurawski et al, 2019). Moreover, biofilms are notorious for their ability to decrease the effectiveness of antibiotic treatment (Hoiby et al, 2010).…”

Section: Biofilms Of Mutant Strains Retain Increased Copper Sensitivitymentioning

confidence: 99%

Characterization of Acinetobacter baumannii Copper Resistance Reveals a Role in Virulence

et al. 2020

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Acinetobacter baumannii is often highly drug-resistant and causes severe infections in compromised patients. These infections can be life threatening due to limited treatment options. Copper is inherently antimicrobial and increasing evidence indicates that copper containing formulations may serve as non-traditional therapeutics against multidrug-resistant bacteria. We previously reported that A. baumannii is sensitive to high concentrations of copper. To understand A. baumannii copper resistance at the molecular level, herein we identified putative copper resistance components and characterized 21 strains bearing mutations in these genes. Eight of the strains displayed a copper sensitive phenotype (pcoA, pcoB, copB, copA/cueO, copR/cusR, copS/cusS, copC, copD); the putative functions of these proteins include copper transport, oxidation, sequestration, and regulation. Importantly, many of these mutant strains still showed increased sensitivity to copper while in a biofilm. Inductively coupled plasma mass spectrometry revealed that many of these strains had defects in copper mobilization, as the mutant strains accumulated more intracellular copper than the wildtype strain. Given the crucial antimicrobial role of copper-mediated killing employed by the immune system, virulence of these mutant strains was investigated in Galleria mellonella; many of the mutant strains were attenuated. Finally, the cusR and copD strains were also investigated in the murine pneumonia model; both were found to be important for full virulence. Thus, copper possesses antimicrobial activity against multidrug-resistant A. baumannii, and copper sensitivity is further increased when copper homeostasis mechanisms are interrupted. Importantly, these proteins are crucial for full virulence of A. baumannii and may represent novel drug targets.

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“…A. baumannii infections are usually very difficult to treat; however, the organism has depicted a relatively low virulence potential in immunocompetent hosts [ 9 ]. However, recently, animal infection models have reported A. baumannii strains with increased pathogenicity [ 10 , 11 ]. This might be due to phenotypic and genetic adaptations that could increase the resistance and virulence potential of A. baumannii [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Virulence Potential and Treatment Options of Multidrug-Resistant (MDR) Acinetobacter baumannii

2021

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Acinetobacter baumannii is an opportunistic pathogen which is undoubtedly known for a high rate of morbidity and mortality in hospital-acquired infections. A. baumannii causes life-threatening infections, including; ventilator-associated pneumonia (VAP), meningitis, bacteremia, and wound and urinary tract infections (UTI). In 2017, the World Health Organization listed A. baumannii as a priority-1 pathogen. The prevalence of A. baumannii infections and outbreaks emphasizes the direct need for the use of effective therapeutic agents for treating such infections. Available antimicrobials, such as; carbapenems, tigecycline, and colistins have insufficient effectiveness due to the appearance of multidrug-resistant strains, accentuating the need for alternative and novel therapeutic remedies. To understand and overcome this menace, the knowledge of recent discoveries on the virulence factors of A. baumannii is needed. Herein, we summarized the role of various virulence factors, including; outer membrane proteins, efflux pumps, biofilm, penicillin-binding proteins, and siderophores/iron acquisition systems. We reviewed the recent scientific literature on different A. baumannii virulence factors and the effective antimicrobial agents for the treatment and management of bacterial infections.

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A Porcine Wound Model ofAcinetobacter baumanniiInfection

Cited by 20 publications

References 65 publications

Recent Advances in the Pursuit of an Effective Acinetobacter baumannii Vaccine

Recent Advances in the Pursuit of an Effective Acinetobacter baumannii Vaccine

Characterization of Acinetobacter baumannii Copper Resistance Reveals a Role in Virulence

Virulence Potential and Treatment Options of Multidrug-Resistant (MDR) Acinetobacter baumannii

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