Abstract
Bacteriophages are viruses that infect bacteria, replicating and multiplying using host resources. For specific infections, bacteriophages have developed extraordinary proteins for recognizing and degrading their host. Inspired by the remarkable development of viral proteins, we used the tail fiber protein to treat multiple drug-resistant Acinetobacter baumannii. The tail fiber protein exhibits polysaccharide depolymerases activity which specifically degrades exopolysaccharide (EPS) during the phage–host interaction. However, EPS-degraded cells are observed altering host susceptibility to bacterial lysis peptide, the endolysin-derived peptide. Notably, endolysin is necessary in the process of progeny liberation by breaking the bacterial cell wall. Surprisingly, peeling the EPS animated host to resist colistin, the last-resort antibiotic used in multidrug-resistant Gram-negative bacteria infection. Tail fiber-modified cell wall reduces colistin attachment, causing temporary antibiotic-resistance and possibly raising clinical risks in treating multiple drug-resistant A. baumannii.
Highlights
Increasing antibiotic abuse led to selective stress, driving the development of multiple drug resistant (MDR) ‘superbugs’, raising the urgent need to screen new antibiotics or develop alternative therapeutic strategies [2]
Morphology and characterization of the nanoparticles and bacteria were monitored by transmission electron microscopy (TEM, Hitachi H-7500) Surface analysis of the bacteria was observed by high-resolution scanning electron microscope (HR-SEM, JEOL JSM-7001F)
tail fiber (TF) treated nontreated) bacteria adhered colistin-fluorescein isothiocyanate (FITC) conjugate was measured under the same parameters
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Based on the phage infection processes, the bacterial host develops various resistance mechanisms for blocking phage absorption, invasion, and propagation [13]. Selectivity against the expression of virulence factors to resist phage infection may attenuate host defense to antibiotics, promoting the development of PAS therapy and realizing the mechanism of action and stoichiometry [19]. A structural study showed TF possesses a bacterial receptor binding domain and an exopolysaccharide (EPS) depolymerization domain [26] Based on these findings, we propose a combination strategy of co-treating MDR A. baumannii with antiobiotics (or phage endolysin derived peptide, P3) and TF molecules. We surprisingly observed a temporary increase in resistance to colistin, used as the last-resort antibiotic for MDR Gram negative bacterial infection. Evaluation of the phage attacking behavior suggests the temporary increased resistance may be associated with an increased risk of drug-resistance during PSA in clinical MDR A. baumannii treatment
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