Abstract
Pathogenic bacterial biofilms play an important role in recurrent nosocomial and medical device-related infections. Once occurred, the complex structure of the biofilm promotes the development of antibiotic resistance and becomes extremely difficult to eradicate. Here we describe a novel and effective anti-biofilm compound maipomycin A (MaiA), which was isolated from the metabolites of a rare actinomycete strain Kibdelosporangium phytohabitans XY-R10. Its structure was deduced from analyses of spectral data and confirmed by single-crystal X-ray crystallography. This natural product demonstrated a broad spectrum of anti-biofilm activities against Gram-negative bacteria. Interestingly, the addition of Fe(II) or Fe(III) ions could block the biofilm inhibition activity of MaiA because it is an iron chelator. However, not all iron chelators showed biofilm inhibition activity, suggesting that MaiA prevents biofilm formation through a specific yet currently undefined pathway. Furthermore, MaiA acts as a synergist to enhance colistin efficacy against Acinetobacter baumannii. Our results indicate that MaiA may potentially serve as an effective antibiofilm agent to prevent Gram-negative biofilm formation in future clinical applications.
Highlights
Bacterial resistance against antibiotics is a global health problem of increasing importance, one of the major mechanisms of resistance is the formation of biofilms by pathogens
We found the crude extract of K. phytohabitans XY-R10 was able to inhibit the biofilm formation of A. baumannii ATCC 19606
These spectroscopic features suggested that maipomycin A (MaiA) belonged to the family of 2, 2 -bipyridyl, and was most similar to pyrisulfoxin A (PyrA), which was isolated as an antibiotic (Tsuge et al, 1999)
Summary
Bacterial resistance against antibiotics is a global health problem of increasing importance, one of the major mechanisms of resistance is the formation of biofilms by pathogens. The biofilms of “ESKAPE” pathogens (Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) commonly present the most acute threat (Ma et al, 2020). Nosocomial infections caused by biofilm forming GNB such as pneumonia, urinary tract infections, endocarditis, wound infection, and bacteremia, are becoming increasingly deadly (Lyczak et al, 2000; Dijkshoorn et al, 2007; Prowle et al, 2011; Frykberg and Banks, 2015). Ventilator-associated pneumonia with a mortality rate as high as 60% (Bertolini et al, 2018), and catheter-associated urinary tract infections with morbidity rate approximately to 70% (Shuman and Chenoweth, 2018) are resulted from biofilmrelated infections mainly caused by A. baumannii, P. aeruginosa, and Enterobacter spp
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