The rising spread of antimicrobial resistance challenges animal welfare, productivity and food supply with respect to bacterial infections in different livestock species. Bacteriophages offer alternative means to control infections with resistant bacteria. This work investigated the host immune responses towards lytic bacteriophages K and T1, acting respectively on Gram-positive or Gram-negative bacteria. We employed an ex vivo platform to decipher various immune responses elicited by primary blood cells of eight outbred cattle. Bacteriophage K was not recognized whereas bacteriophage T1 induced a profound immune response. Therefore, prior characterization of host immune responses towards therapeutic phages should be considered before therapy starts.

Phage therapy shows promise as an adjunct to antibiotics for treating Staphylococcus aureus infections. We previously reported a combined flucloxacillin/two-phage cocktail treatment selected for resistance to podovirus phage 66 in a rodent model of methicillin-susceptible S. aureus (MSSA) endocarditis. Here we show that resistant clones harbor mutations in tarS, which encodes a glycosyltransferase essential for β-GlcNAcylation of wall teichoic acid (WTA). This WTA modification has been described in vitro as critical for podoviruses adsorption. Transcriptomics confirmed continued tarS expression in resistant clones, supporting a loss-of-function mechanism. Accordingly, phage 66 binding and killing were restored by WT tarS complementation. In addition, we investigated the counterintuitive innate susceptibility to phage 66 of the tarM + Laus102 strain used in the endocarditis model. We show that it likely results from a significant lower tarM expression, in contrast to the innate resistant strain RN4220. Our findings demonstrate that tarS-mediated WTA β-GlcNAcylation is critical for podovirus infection also in vivo and identify tarM transcriptional defect as a new mechanism of podoviruses susceptibility in S. aureus. Moreover, and since tarS disruption has been previously shown to enhance β-lactam susceptibility, our results support the development of combined podovirus/antibiotic strategies for the management of MRSA infections.

Colibacillosis, caused by avian pathogenic Escherichia coli (APEC), affects the poultry industry worldwide. APEC infections impact food supply, especially in low- and middle-income countries, and more knowledge on APEC diversity will foster research towards better control measures. Here, we present the complete genomes of three APEC strains isolated in Pakistan.

Avian pathogenic Escherichia coli , including strains that are resistant to antimicrobials, negatively impacts the poultry industry worldwide and the provision of animal protein to the people. Here, we report the complete genomes of the lytic bacteriophage PBM-3 and its bacterial host PE144, both isolated in Pakistan.