Bacteria can be adapted to adverse and detrimental conditions that induce general and specific responses to DNA damage as well as acid, heat, cold, starvation, oxidative, envelope, and osmotic stresses. The stress-triggered regulatory systems are involved in bacterial survival processes, such as adaptation, physiological changes, virulence potential, and antibiotic resistance. Antibiotic susceptibility to several antibiotics is reduced due to the activation of stress responses in cellular physiology by the stimulation of resistance mechanisms, the promotion of a resistant lifestyle (biofilm or persistence), and/or the induction of resistance mutations. Hence, the activation of bacterial stress responses poses a serious threat to the efficacy and clinical success of antibiotic therapy. Bacterial stress responses can be potential targets for therapeutic alternatives to antibiotics. An understanding of the regulation of stress response in association with antibiotic resistance provides useful information for the discovery of novel antimicrobial adjuvants and the development of effective therapeutic strategies to control antibiotic resistance in bacteria. Therefore, this review discusses bacterial stress responses linked to antibiotic resistance in Gram-negative bacteria and also provides information on novel therapies targeting bacterial stress responses that have been identified as potential candidates for the effective control of Gram-negative antibiotic-resistant bacteria.

The rapid emergence and spread of antibiotic-resistant bacteria continues to be an issue difficult to deal with, especially in the clinical, animal husbandry, and food fields. The occurrence of multidrug-resistant bacteria renders treatment with antibiotics ineffective. Therefore, the development of new therapeutic methods is a worthwhile research endeavor in treating infections caused by antibiotic-resistant bacteria. Recently, bacterial membrane vesicles (BMVs) have been investigated as a possible approach to drug delivery and vaccine development. The BMVs are released by both pathogenic and non-pathogenic Gram-positive and Gram-negative bacteria, containing various components originating from the cytoplasm and the cell envelope. The BMVs are able to transform bacteria with genes that encode enzymes such as proteases, glycosidases, and peptidases, resulting in the enhanced antibiotic resistance in bacteria. The BMVs can increase the resistance of bacteria to antibiotics. However, the biogenesis and functions of BMVs are not fully understood in association with the bacterial pathogenesis. Therefore, this review aims to discuss BMV-associated antibiotic resistance and BMV-based therapeutic interventions.

Biofilms remain a major challenge in the food industry due to the increased resistance of foodborne pathogens to antimicrobial agents and food processing stresses, leading to food contamination and significant health risks. Their resistance to preservation techniques, antimicrobial treatments, and processing conditions increases concerns regarding food safety. This review discusses recent developments in physical, chemical, and surface modification strategies to control and remove biofilms in food processing environments. Physical methods, such as thermal treatments, electric fields, and ultrasonic systems, have demonstrated their efficacy in disrupting biofilm structure and improving disinfection processes. Chemical treatments, including the use of sanitizers, disinfectants, acidulants, and enzymes, provide targeted approaches to degrade biofilm matrices and inhibit bacterial adhesion. Furthermore, surface modifications of food contact materials provide innovative solutions for preventing biofilm formation and enhancing food safety. These cutting-edge strategies not only improve food safety but also reduce contamination risk in food processing facilities. The review highlights the mechanisms, efficacy, and applicability of these techniques, emphasizing their potential to mitigate biofilm-associated risks and ensure food quality and safety.

This study was designed to assess the influence of efflux pump activity on the biofilm formation in Salmonella Typhimurium. Salmonella enterica subsp. enterica serovar Typhimurium ATCC 19585 (ST^WT) and clinically isolated S. Typhimurium CCARM 8009 (ST^CI) were treated with ceftriaxone (CEF), chloramphenicol (CHL), ciprofloxacin (CIP), erythromycin (ERY), norfloxacin (NOR), and tetracycline (TET) in autoinducer-containing media in the absence and presence of phenylalanine-arginine β-naphthylamide (PAβN) to compare efflux pump activity with biofilm-forming ability. The susceptibilities of ST^WT and ST^CI were increased in the presence of PAβN. ERY+PAβN showed the highest decrease in the minimum inhibitory concentration (MIC) of ERY from 256 to 2 μg/mL against ST^WT and ST^CI. The antimicrobial activity of NOR against planktonic cells was significantly increased in the presence of PAβN, showing the lowest numbers of ST^WT (3.2 log CFU/cm²), and the TET+PAβN effectively inhibited the growth of ST^CI (5.2 log CFU/cm²). The lowest biofilm-forming abilities were observed at NOR+PAβN against ST^WT (biofilm-forming index, BFI < 0.41) and CEF+PAβN against ST^CI (BFI = 0.32). The bacteria swimming motility and relative fitness varied depending on the antibiotic and PAβN treatments. The motility diameters of ST^WT were significantly decreased by NOR+PAβN (6 mm) and TET+PAβN (15 mm), while the lowest motility of ST^CI was observed at CIP+PAβN (8 mm). The significant decrease in the relative fitness levels of ST^WT and ST^CI was observed at CIP+PAβN and NOR+PAβN. The PAβN as an efflux pump inhibitor (EPI) can improve the antimicrobial and anti-biofilm efficacy of antibiotics against S. Typhimurium. This study provides useful information for understanding the role of efflux pump activity in quorum sensing-regulated biofilm formation and also emphasizes the necessity of the discovery of novel EPIs for controlling biofilm formation by antibiotic-resistant pathogens.

This study was designed to evaluate the stability of chloramphenicol, erythromycin, tetracycline, cephalothin, ciprofloxacin, and tobramycin against antibiotic-sensitive Salmonella Typhimurium (ASST) and antibiotic-resistant S. Typhimurium (ARST) during the broth microdilution assay. The antimicrobial activity in association with antibiotic stability was measured by using antibiotic susceptibility, time-delayed inoculation, time-extended incubation, and inoculum effect assays. The loss of the antimicrobial activity of cephalothin against ASST exposed to 1 MIC was observed for the 10 h delayed inoculation. The antimicrobial activities of tetracycline and ciprofloxacin against ASST and ARST exposed to ½ MIC were significantly decreased after the 10 h delayed inoculation. All antibiotics used in this study, except for ciprofloxacin, showed the considerable losses of antimicrobial activities against ASST and ARST after 40 h of incubation at 37 °C when compared to the 20 h of incubation during AST. Compared to the standard inoculum level (6 log CFU/mL), the MIC_0.1 values of bactericidal antibiotics, ciprofloxacin and tobramycin against ASST were increased by more than 4-fold at the high inoculum level of 9 log CFU/mL. This would provide practical information for better understanding the clinical efficacy of the currently used antibiotics by considering the antibiotic stability during incubation time at different inoculum levels.