Bacterial antibiotic resistance, especially the emergence of multidrug-resistant (MDR) strains, urgently requires the development of effective treatment strategies. It is always of interest to delve into the mechanisms of resistance to current antibiotics and target them to promote the efficacy of existing antibiotics. In recent years, non-antibiotic compounds have played an important auxiliary role in improving the efficacy of antibiotics and promoting the treatment of drug-resistant bacteria. The combination of non-antibiotic compounds with antibiotics is considered a promising strategy against MDR bacteria. In this review, we first briefly summarize the main resistance mechanisms of current antibiotics. In addition, we propose several strategies to enhance antibiotic action based on resistance mechanisms. Then, the research progress of non-antibiotic compounds that can promote antibiotic-resistant bacteria through different mechanisms in recent years is also summarized. Finally, the development prospects and challenges of these non-antibiotic compounds in combination with antibiotics are discussed.

Intestinal inflammation is a chronic gastrointestinal disorder with uncertain pathophysiology and causation that has significantly impacted both the physical and mental health of both people and animals. An increasing body of research has demonstrated the critical role of cellular signaling pathways in initiating and managing intestinal inflammation. This review focuses on the interactions of three cellular signaling pathways (TLR4/NF-κB, PI3K-AKT, MAPKs) with immunity and gut microbiota to explain the possible pathogenesis of intestinal inflammation. Traditional medicinal drugs frequently have drawbacks and negative side effects. This paper also summarizes the pharmacological mechanism and application of Chinese herbal compounds (Berberine, Sanguinarine, Astragalus polysaccharide, Curcumin, and Cannabinoids) and formulae (Wumei Wan, Gegen-Qinlian decoction, Banxia xiexin decoction) against intestinal inflammation. We show that the herbal compounds and formulae may influence the interactions among cell signaling pathways, immune function, and gut microbiota in humans and animals, exerting their immunomodulatory capacity and anti-inflammatory and antimicrobial effects. This demonstrates their strong potential to improve gut inflammation. We aim to promote herbal medicine and apply it to multispecies animals to achieve better health.

Allocryptopine (ALL) is an isoquinoline alkaloid extracted from Macleaya cordata(Willd). R. Br., which has been claimed to have anti-inflammatory and neuroprotection properties. However, the mechanism by which ALL ameliorates inflammatory bowel disease (IBD) remains unclear. Here, we used network pharmacology and quantitative proteomic approaches to investigate the effect of ALL on IBD pathogenesis. Network pharmacology predicted potential targets and signaling pathways of ALL’s anti-IBD effects. As predicted by network pharmacology, gene ontology (GO) analysis, in terms of the proteomic results, showed that the immune response in mucosa and antimicrobial humoral response were enriched. Further study revealed that the ALL-related pathways were the chemokine signaling pathway and apoptosis in the Kyoto Encyclopedia of Genes and Genomes (KEGG). In addition, we identified AKT1 as a hub for the critical pathways through protein–protein interaction (PPI) network analysis. Similar to mesalazine (MES), Western blot verified that ALL downregulated upstream chemokine CX3CL1 and GNB5 content to reduce phosphorylation of AKT and NF-κB, as well as the degree of apoptosis, to improve inflammatory response in the colon. Our research may shed light on the mechanism by which ALL inhibits the CX3CL1/GNB5/AKT2/NF-κB/apoptosis pathway and improves the intestinal barrier to reduce colitis response and act on the CX3CL1–CX3CR1 axis to achieve neuroprotection.

Background: The plasmid−mediated tigecycline resistance gene tet(X4) confers a high level of resistance to tigecycline. The experiment aims to investigate the prevalence and characterization of tet(X4) in Escherichia coli isolates from chicken and pig farms in Hunan province, China. Methods: A total of six tet(X4) positive strains were identified in 257 E. coli derived from chicken samples in Xiangtan city (n = 2), pig samples in Xiangxiang city (n = 1), Chenzhou city (n = 2), and Zhuzhou city (n = 1). The presence of tet(X4) was directly detected by PCR assay, and then the broth dilution method determined the antimicrobial susceptibility profile of the tet(X4)−positive isolates. Genomic locations were identified by whole−genome sequencing (WGS) and bioinformatics. Results: Almost all tet(X4)−positive strains showed high resistance to multidrug, including tigecycline. Resistome analysis revealed many antibiotic resistance genes, including those with resistance to tetracyclines, β−lactams, phenicols, quinolones, lincosamides chloramphenicol, aminoglycosides and sulfamids. These tet(X4)−bearing strains exhibited six distract STs, such as ST10, 202, ST218, ST362, ST2077, ST7068. The plasmid replicon types carrying tet(X4) were the hybrid plasmid IncFIA(HI1)/IncHIA/IncHIB(R27) (5/6) and IncX1 (1/6). Conclusions: The presence of similar genetic environments in E. coli from different cities suggests there may be horizontal transmission pathways promoting the broad spread of drug−resistant genes in Hunan Province, putting great pressure on multidrug resistance monitoring.

Multi-drug resistance of bacteria producing extended-spectrum β-lactamase (ESBL) is a public health challenge. Thus, this study aimed to investigate the antimicrobial susceptibility of ESBL-producing Escherichia coli (ESBL-EC) in Hunan Province, China. A total of 1366 fecal samples were collected from pig, chicken, and cattle farms over a six-year period, which were assessed using strain isolation, 16S rRNA identification, polymerase chain reaction, drug sensitivity testing, whole-genome sequencing, and bioinformatics analysis. The results showed an overall prevalence of 6.66% for ESBL-EC strains, with ESBL positivity extents for pigs, chickens, and cattle isolates at 6.77%, 6.54%, and 12.5%, respectively. Most ESBL-EC isolates were resistant to cefotaxime, tetracycline, and trimethoprim-sulfamethoxazole; however, all the isolates were susceptible to meropenem, with relatively low resistance to amikacin and tigecycline. Various multi-locus sequence types with different origins and similar affinities were identified, with ST155 (n = 16) being the most common subtype. Several types of resistance genes were identified among the 91 positive strains, with beta-lactamase bla_CTX-M-55 being the most common ESBL genotype. IncFIB was the predominant plasmid type. Widespread use of antibiotics in animal farming may increase antibiotic resistance, posing a serious threat to the health of farmed animals and, thus, to human food security and health.