Abstract
Increasing antimicrobial resistance due to misuse and overuse of antimicrobials, as well as a lack of new and innovative antibiotics in development has become an alarming global threat. Preventative therapeutics, like vaccines, are combative measures that aim to stop infections at the source, thereby decreasing the overall use of antibiotics. Infections due to Gram-negative pathogens pose a significant treatment challenge because of substantial multidrug resistance that is acquired and spread throughout the bacterial population. Burkholderia spp. are Gram-negative intrinsically resistant bacteria that are responsible for environmental and nosocomial infections. The Burkholderia cepacia complex are respiratory pathogens that primarily infect immunocompromised and cystic fibrosis patients, and are acquired through contaminated products and equipment, or via patient-to-patient transmission. The Burkholderia pseudomallei complex causes percutaneous wound, cardiovascular, and respiratory infections. Transmission occurs through direct exposure to contaminated water, water-vapors, or soil, leading to the human disease melioidosis, or the equine disease glanders. Currently there is no licensed vaccine against any Burkholderia pathogen. This review will discuss Burkholderia vaccine candidates derived from outer membrane proteins, OmpA, OmpW, Omp85, and Bucl8, encompassing their structures, conservation, and vaccine formulation.
Highlights
Following the “Golden Age” of antibiotic discovery, antibiotic resistance quickly arose in tandem, resulting in the emergence of antimicrobial resistant (AMR) bacteria
Outer membrane protein A (OmpA) has been evaluated as a vaccine candidate in several concerning Gram-negative pathogens, including E. coli [61], A. baumannii [62], P. aeruginosa [63,64], and Burkholderia spp. [65,66]
Like OmpA, OmpW is a common outer membrane proteins (OMPs) found in Gram-negative bacteria, and evidence of its immunogenicity dates back to 1980 s, when it was first described as immunoreactive determinant with sera from patients infected with Vibrio cholerae [71,72]
Summary
Following the “Golden Age” of antibiotic discovery, antibiotic resistance quickly arose in tandem, resulting in the emergence of antimicrobial resistant (AMR) bacteria. The “ESKAPE” pathogens, made up of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp., were recognized by the Centers for Disease Control and Prevention as the highly multidrug resistant bacteria of the greatest concern [1]. Multidrug resistant Burkholderia spp., responsible for infections in patients with cystic fibrosis or melioidosis, are of rising concern due to their intrinsic multidrug resistance, increased globalization, and problems with identification, reporting, and treatment [2,3,4]. Prophylactic medical countermeasures such as vaccines, are an attractive treatment option against MDR bacteria to stop infection before it starts. We will highlight outer membrane proteins (OMPs) as vaccine targets of Burkholderia-derived antigens
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