The aim of this study was to investigate the antimicrobial resistance profiles and genotypes of Streptococcus suis in Heilongjiang Province, China. A total of 29 S. suis were isolated from 332 samples collected from 6 pig farms. The results showed that serotypes 2, 4 and 9 were prevalent, and all the clinical isolates were resistant to at least two antibacterial drugs. The most resisted drugs were macrolides, and the least resisted drugs were fluoroquinolones. Resistant genes ermB and aph (3′)-IIIa were highly distributed among the isolates, with the detection rates of 79.31% and 75.86%. The formation of biofilm could be observed in all the isolated S. suis, among which D-1, LL-1 and LL-3 strains formed stronger biofilm structure than other strains. The results indicate that S. suis in Heilongjiang Province presents a multi-drug resistance to commonly used antimicrobial drugs, which was caused by the same target gene, the dissemination of drug resistance genes, and bacterial biofilm.

Staphylococcus aureus poses a significant global threat to both human and animal health. Bacterial-targeted therapies are limited by strong selective pressures (e.g., mecA-mediated β-lactam resistance) and the pathogen's remarkable capacity for phagocyte intracellular survival-a strategy that allows them to evade antibiotics and the immune system, ultimately leading to persistent infections. These factors highlight the urgent need for alternative strategies to combat bacterial infections. This review explores host-directed therapies (HDTs) as alternative strategies for combating S. aureus infections, aiming to overcome limitations of current treatments and contribute to the development of novel or combination therapies. HDTs offer several advantages, including a reduced risk of bacterial resistance, a broad antimicrobial spectrum, and the potential for synergy with antibiotics to shorten treatment duration and even treat persistent intracellular infections. Target-based precision drug design shows strong promise in addressing off-target effect challenges. This review provides an overview of key host factors involved in S. aureus pathogenesis, emphasizing therapeutic agents targeting these factors, their mechanisms of action, and pharmacological profiles. These recent advancements are crucial in the ongoing efforts to combat S. aureus infections.

The emergence and rapid development of antibiotic resistance poses a serious threat to global public health. Streptococcus suis (S. suis) is an important zoonotic pathogen, and the development of its antibiotic resistance has made the infections difficult to treat. The combination of non-antibiotic compounds with antibiotics is considered a promising strategy against multidrug-resistant bacteria. However, the mechanism by which metabolites act as antibiotic adjuvant remains unclear. Here, we found that guanosine metabolism was repressed in multidrug-resistant S. suis. Exogenous guanosine promoted the antibacterial effects of ceftiofur sodium (CEF) in vitro and in vivo. Furthermore, we demonstrated that exogenous guanosine promoted the biosynthesis of purine pathway, TCA cycle and bacterial respiration, which make bacteria more sensitive to the killing effect of antibacterial. In addition, the function of the cell membrane is affected by guanosine and the accumulation of antimicrobials in the bacteria increased. Bacterial-oxidative stress and DNA damage induced by guanosine is also one of the mechanisms by which the antibacterial effect is enhanced. These results suggest that guanosine is a promising adjuvant for antibacterial drugs and provide new theoretical basis for the clinical treatment of S. suis infection.