Efficacy of Treatment with the Antibiotic Novobiocin against Infection with Bacillus anthracis or Burkholderia pseudomallei

• Published in: Antibiotics (Basel) Vol. 11; no. 12; p. 1685
• Main Authors: Klimko, Christopher P, Welkos, Susan L, Shoe, Jennifer L, Mou, Sherry, Hunter, Melissa, Rill, Nathaniel O, DeShazer, David, Cote, Christopher K
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 23-11-2022; MDPI
• Subjects: Aerosols; Animal diseases; Animal models; Anthrax; Antibiotic resistance; Antibiotics; Antimicrobial agents; Bacillus anthracis; Bacteria; biothreats; Brief Report; broad spectrum; Burkholderia pseudomallei; Disease; Drug resistance; early-generation antibiotics; Effectiveness; Gram-negative bacteria; Health services; Infections; Inhalation; Melioidosis; Microorganisms; Mortality; Novobiocin; Pathogens; Respiration; Sepsis; Survival analysis; Vaccination; biothreats; Bacillus anthracis; novobiocin; Burkholderia pseudomallei; melioidosis; early-generation antibiotics; anthrax; mice; broad spectrum
• ISSN: 2079-6382; 2079-6382
• DOI: 10.3390/antibiotics11121685

The microbial pathogens
and
are unrelated bacteria, yet both are the etiologic agents of naturally occurring diseases in animals and humans and are classified as Tier 1 potential biothreat agents.
is the gram-negative bacterial agent of melioidosis, a major cause of sepsis and mortality globally in endemic tropical and subtropical regions.
is the gram-positive spore-forming bacterium that causes anthrax. Infections acquired by inhalation of these pathogens are challenging to detect early while the prognosis is best; and they possess innate multiple antibiotic resistance or are amenable to engineered resistance. Previous studies showed that the early generation, rarely used aminocoumarin novobiocin was very effective in vitro against a range of highly disparate biothreat agents. The objective of the current research was to begin to characterize the therapeutic efficacy of novobiocin in mouse models of anthrax and melioidosis. The antibiotic was highly efficacious against infections by both pathogens, especially
. Our results supported the concept that specific older generation antimicrobials can be effective countermeasures against infection by bacterial biothreat agents. Finally, novobiocin was shown to be a potential candidate for inclusion in a combined pre-exposure vaccination and post-exposure treatment strategy designed to target bacterial pathogens refractory to a single medical countermeasure.