Polysaccharide depolymerase, a polysaccharide hydrolase encoded by bacteriophages (or 'phages'), can specifically degrade the macromolecule carbohydrates of the host bacterial envelope. This enzyme assists the bacteriophage in adsorbing, invading, and disintegrating the host bacteria. Polysaccharide depolymerase activity continues even within biofilms. This effectiveness means phages are promising candidates for novel antibiotic scaffolds. A comprehensive compendium of bacteriophage polysaccharide depolymerases has been compiled, together with their potential biomedical applications, such as novel antibiotics, adjuvants for antibiotics, bacterial biofilm disruptants, and diagnostic kits.

M. tuberculosis is intrinsically tolerant to many antibiotics largely due to the imperviousness of its unusual mycolic acid-containing cell wall to most antimicrobials. The emergence and increasingly widespread of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) revitalized keen interest in phage-inspired therapy. SWU1gp39 is a novel gene from mycobacteriophage SWU1 with unknown function. SWU1gp39 expressed in M. smegmatis conferred the host cell increased susceptibility to multiple antibiotics, including isoniazid, erythromycin, norfloxacin, ampicillin, ciprofloxacin, ofloxacin, rifampicin and vancomycin, and multiple environment stresses such as H2O2, heat shock, low pH and SDS. By using EtBr/Nile red uptake assays, WT-pAL-gp39 strain showed higher cell wall permeability than control strain WT-pAL. Moreover, the WT-pAL-gp39 strain produced more reactive oxygen species and reduced NAD+/NADH ratio. RNA-Seq transcriptomes of the WT-pAL-gp39 and WT-pAL revealed that the transcription of 867 genes was differentially regulated, including genes associated with lipid metabolism. Taken together, our results implicated that SWU1gp39, a novel gene from mycobacteriophage, disrupted the lipid metabolism of host and increased cell wall permeability, ultimately potentiated the efficacy of multiple antibiotics and stresses against mycobacteria.

Mycobacteriophage SWU1 is a newly isolated phage from soil sample collected in Sichuan province, China using Mycobacterium smegmatis mc2155 as host. Plaque, phage morphology and one-step growth curve were characterized. The complete genomic sequence of phage SWU1 was determined by shotgun sequencing. The ends of SWU1 were determined. Structural proteins of SWU1 were analyzed by NanoLC-ESI-MS/MS. Seven ORFs were identified as structural protein encoded by SWU1 genome. The genetic basis underlying the SWU1 plaque was explored using comparative genomics. Prophages homologous to SWU1 were identified in two pathogens, Segniliparus rugosus ATCC BAA-974 and Mycobacterium rhodesiae JS60. Genus Segniliparus is a member of the order Corynebacteriales. To our knowledge, this is the first report of Mycobacterium prophages in different genera.

Ribosome, the protein synthesis machinery essential for all living cells, consists of ribosomal proteins and RNA. Extraribosomal functions have recently been discovered for many ribosomal proteins, acting either as individual regulatory proteins or as a complex with other cell components. However, extraribosomal functions of Mycobacterium tuberculosis ribosomal proteins have not been systematically addressed. To this end, M. tuberculosis ribosomal proteins potentially engaged in extraribosomal functions were curated by data mining from transcriptional profiles of M. tuberculosis exposed to diverse treatments. Six M. tuberculosis ribosomal proteins, namely, S3 (Rv0707, rpsC), L16 (Rv0708, rplP), L29 (Rv0709, rpmC), S17 (Rv0710, rpsQ), S14 (Rv2056c, rpsN2), and L33 (Rv2057c, rpmG1), were found to behave idiosyncratically. The function of these abnormal ribosomal subunits can be further explored. Special emphasis is on their potential value as novel targets for better antibiotics.

Bacteriophage is bacterial virus widespread in the biosphere. Bacteriophages and their encoded endolysin (or lysin), holin, and other small proteins are intensively pursed as novel therapeutic agents to complement and tackle the increasing antibiotics resistance. Moreover, the delivery system based on bacteriophage and the diagnostic method based on engineered bacteriophage were also promising new avenues to drug delivery and diagnosis.