Therapeutic phages are being employed for vaccination and treatment of cancer and bacterial infections. Their natural immunogenicity triggers intertwined interactions with innate and adaptive immune cells that might influence therapy. Phage- and bactierial-derived pathogen-associated molecular patterns released after bacterial lysis have been proposed to stimulate local innate immune responses, which could promote antitumor immunity or bacterial clearance. Conversely, immunogenicity of phages induces phage-specific humoral memory, which can hamper therapeutic success. This review outlines the current knowledge on the different types of immune responses elicited by phages and their potential benefits and adverse side effects, when applied therapeutically. This review further summarizes the knowledge gaps and defines the key immunological questions that need to be addressed regarding the clinical application of antibacterial phage therapy.

Livestock-associated bacteria with resistance to two or more antibiotic drug classes have heightened our awareness for the consequences of antibiotic consumption and spread of resistant bacterial strains in the veterinary field. In this study we assessed the prevalence of concomitant colonization with livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) and enterobacteriaceae expressing extended-spectrum betalactamases (ESBL-E) in farms at the German-Dutch border region. Nasal colonization of pigs with MRSA (113/547 (20.7%)) was less frequent than rectal colonization with ESBL-E (163/540 (30.2%)). On the individual farm level MRSA correlated with ESBL-E recovery. The data further provide information on prevalence at different stages of pig production, including abattoirs, as well as in air samples and humans living and working on the farms. Notably, MRSA was detected in stable air samples of 34 out of 35 pig farms, highlighting air as an important MRSA transmission reservoir. The majority of MRSA isolates, including those from humans, displayed tetracycline resistance and spa types t011 and t034 characteristic for LA-MRSA, demonstrating transmission from pigs to humans. ESBL-E positive air samples were detected on 6 out of 35 farms but no pig-to-human transmission was found. Detection of ESBL-E, e.g. mostly Escherichia coli with CTX-M-type ESBL, was limited to these six farms. Molecular typing revealed transmission of ESBL-E within the pig compartments; however, related strains were also found on unrelated farms. Although our data suggest that acquisition of MRSA and ESBL-E might occur among pigs in the abattoirs, MRSA and ESBL-E were not detected on the carcasses. Altogether, our data define stable air (MRSA), pig compartments (ESBL-E) and abattoir waiting areas (MRSA and ESBL-E) as major hot spots for transmission of MRSA and/or ESBL-E along the pig production chain.

Lipoproteins (Lpp) of Gram-positive bacteria are major players in alerting our immune system. Here, we show that the TLR2 response induced by commensal species Staphylococcus aureus and Staphylococcus epidermidis is almost ten times lower than that induced by noncommensal Staphylococcus carnosus, and this is at least partially due to their different modifications of the Lpp lipid moieties. The N terminus of the lipid moiety is acylated with a long-chain fatty acid (C17) in S. aureus and S. epidermidis, while it is acylated with a short-chain fatty acid (C2) in S. carnosus. The long-chain N-acylated Lpp, recognized by TLR2–TLR1 receptors, silences innate and adaptive immune responses, while the short-chain N-acetylated Lpp, recognized by TLR2–TLR6 receptors, boosts it.

Objective: This retrospective surveillance study aimed to follow periodontitis‐associated bacterial profiles and to identify time‐dependent changes in antibiotic susceptibility patterns.Materials and Methods: From 2008 to 2015, bacterial specimen from deep periodontal pockets were collected from a total of 7804 German adults diagnosed with periodontitis. Presence of selected bacteria was confirmed by anaerobic culture and nucleic acid amplification. Antimicrobial susceptibility of clinical isolates was tested by disc diffusion with antibiotics used for the treatment of periodontitis and oral infections. The prevalences of periodontal pathogens were calculated and temporal evolution of antimicrobial susceptibility towards amoxicillin, amoxicillin/clavulanic acid, metronidazole, doxycycline, clindamycin, azithromycin, ciprofloxacin and ampicillin was analysed with logistic regression.Results: The prevalence of patients harbouring bacteria was 95.9% Fusobacterium nucleatum, 88.0% Tannerella forsythia, 76.4% Treponema denticola, 76.5%, Campylobacter rectus, 76.0% Eikenella corrodens, 75.0% Capnocytophaga spp., 68.2% Porphyromonas gingivalis, 57.7% Peptostreptococcus micros, 43.1% Prevotella intermedia, 30.4% Eubacterium nodatum and 21.5% Aggregatibacter actinomycetemcomitans. In 63.5% of patients, one or more isolates were not susceptible to at least one of the antibiotics tested. The data further revealed a trend towards decreasing susceptibility profiles (p < 0.05) with antibiotic non‐susceptibilities in 37% of patients in 2008 and in 70% in 2015.Conclusions: The present study confirmed a high prevalence of periodontal pathogens in the subgingival microbiota of German periodontitis patients. The data revealed an incremental increase in isolates displaying resistance to some antibiotics but no relevant change in susceptibility to amoxicillin and metronidazole.