Acinetobacter baumannii plays a significant role in infecting patients admitted to hospitals. Many A. baumannii infections, including ventilation-associated pneumonia, wound, and bloodstream infections, are common for intensive care and burn units. The ability of the microorganism to acquire resistance to many antibiotics, disinfectants, and dehydration assures its long-term survival in hospital settings. The application of bacteriophages is a potential tool to control A. baumannii infections. Bacteriophage AP22 lytic for A. baumannii was isolated from clinical materials and classified as a member of the Myoviridae family. The phage had an icosahedral head of 64 nm in diameter and a contractile tail of 85-90 nm in length. According to restriction analysis, AP22 had 46-kb double-stranded DNA genome. The phage AP22 exhibited rapid adsorption (> 99% adsorbed in 5 min), a large burst size (240 PFU per cell), and stability to the wide range of pH. The bacteriophage was shown to specifically infect and lyse 68% (89 of 130) genotype-varying multidrug-resistant clinical A. baumannii strains by forming clear zones. Thus, it could be used as a candidate for making up phage cocktails to control A. baumannii-associated nosocomial infections.
Summary. Insertion mutagenesis with the help of the plasmid pFS23 was used to generate Yersinia pestis fra mutants. The results of pFra-strain production under non-selective conditions suggested that such Y . pestis variants may be generated in natural plague foci at high frequency and may participate in supporting the epizootic process. Present data suggest that the reduction of virulence in Fra-strains reported by the majority of investigators was connected with the use of Y. pestis variants carrying additional unidentified mutations. It was shown that the loss of the ability to produce capsular antigen (FI) alone or in combination with absence of murine toxin production did not lead to an increase in LD50 absolute values. Simultaneous loss of these two virulence determinants did not influence the duration of survival of the infected animals. However, absence of only FI antigen production in the infecting strain resulted in prolonged survival of the infected animals. Conversion of plague infection from acute to chronic form is probably dependent on the animal host species and the Y. pestis parent strain subjected to mutagenesis.
Bacteriophages and phage enzymes are considered as possible alternatives to antibiotics in the treatment of infections caused by antibiotic-resistant bacteria. Due to the ability to cleave the capsular polysaccharides (CPS), one of the main virulence factors of Klebsiella pneumoniae, phage depolymerases, has potential in the treatment of K. pneumoniae infections. Here, we characterized in vivo two novel phage-encoded polysaccharide depolymerases as therapeutics against clinical isolates of K. pneumoniae. The depolymerases Dep_kpv79 and Dep_kpv767 encoded by Klebsiella phages KpV79 (Myoviridae; Jedunavirus) and KpV767 (Autographiviridae, Studiervirinae, Przondovirus), respectively, were identified as specific β-galactosidases that cleave the K. pneumoniae K57 type CPS by the hydrolytic mechanism. They were found to be highly effective at combating sepsis and hip infection caused by K. pneumoniae in lethal mouse models. Here, 80–100% of animals were protected against death by a single dose (e.g., 50 μg/mouse) of the enzyme injected 0.5 h after infection by K. pneumoniae strains of the K57 capsular type. The therapeutic effect of the depolymerases is because they strip the capsule and expose the underlying bacterium to the immune attack such as complement-mediated killing. These data provide one more confirmation that phage polysaccharide depolymerases represent a promising tool for antimicrobial therapy.
Clostridium perfringens is a Gram-positive, spore-forming anaerobic bacterium responsible for human food-borne disease as well as non-food-borne human, animal and poultry diseases. Because bacteriophages or their gene products could be applied to control bacterial diseases in a species-specific manner, they are potential important alternatives to antibiotics. Consequently, poultry intestinal material, soil, sewage and poultry processing drainage water were screened for virulent bacteriophages that lysed C. perfringens. Two bacteriophages, designated ΦCPV4 and ΦZP2, were isolated in the Moscow Region of the Russian Federation while another closely related virus, named ΦCP7R, was isolated in the southeastern USA. The viruses were identified as members of the order Caudovirales in the family Podoviridae with short, non-contractile tails of the C1 morphotype. The genomes of the three bacteriophages were 17.972, 18.078 and 18.397 kbp respectively; encoding twenty-six to twenty-eight ORF's with inverted terminal repeats and an average GC content of 34.6%. Structural proteins identified by mass spectrometry in the purified ΦCP7R virion included a pre-neck/appendage with putative lyase activity, major head, tail, connector/upper collar, lower collar and a structural protein with putative lysozyme-peptidase activity. All three podoviral bacteriophage genomes encoded a predicted N-acetylmuramoyl-L-alanine amidase and a putative stage V sporulation protein. Each putative amidase contained a predicted bacterial SH3 domain at the C-terminal end of the protein, presumably involved with binding the C. perfringens cell wall. The predicted DNA polymerase type B protein sequences were closely related to other members of the Podoviridae including Bacillus phage Φ29. Whole-genome comparisons supported this relationship, but also indicated that the Russian and USA viruses may be unique members of the sub-family Picovirinae.
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