Bacterial histidine kinase (BHK) is a constituent of the two-component signaling (TCS) pathway, which is responsible for the regulation of a number of processes connected to bacterial pathogenicity, virulence, biofilm development, antibiotic resistance, and bacterial persistence. As BHK regulation is diverse, inhibitors can be developed, such as antibiotic synergists, bacteriostatic/bactericidal agents, virulence inhibitors, and biofilm inhibitors. Inhibition of essential BHK has always been an amenable strategy due to the conserved binding sites of the domains across bacterial species and growth dependence. Hence, an inhibitor of BHK might block multiple TCS regulatory networks. This review describes the TCS system and the role of BHK in bacterial virulence and discusses the available inhibitors of BHK, which is a specific response regulator with essential structural features.

Our study focused exclusively on analyzing Escherichia coli (E. coli) contamination in fresh raw mussels and ready-to-eat (RTE) stuffed mussels obtained from authorized and regulated facilities. However, it is critical to recognize that such contamination represents a significant public health threat in regions where unauthorized harvesting and sales practices are prevalent. This study aimed to comprehensively assess the prevalence, molecular characteristics, and antibacterial resistance profiles of E. coli in fresh raw mussels and RTE stuffed mussels. E. coli counts in fresh raw mussel samples ranged from 1 to 2.89 log CFU/g before cooking, with a significant reduction observed post-cooking. RTE stuffed mussel samples predominantly exhibited negligible E. coli presence (<1 log CFU/g). A phylogenetic analysis revealed a dominance of phylogroup A, with variations in the distribution observed across different sampling months. Antibacterial resistance was prevalent among the E. coli isolates, notably showing resistance to ampicillin, streptomycin, and cefotaxime. Extended-spectrum β-lactamase (ESβL) production was rare, with only one positive isolate detected. A variety of antibacterial resistance genes, including tetB and sul1, were identified among the isolates. Notably, virulence factor genes associated with pathogenicity were absent. In light of these findings, it is imperative to maintain rigorous compliance with quality and safety standards at all stages of the mussel production process, encompassing harvesting, processing, cooking, and consumption. Continuous monitoring, implementation of rigorous hygiene protocols, and responsible antibacterial drug use are crucial measures in mitigating food safety risks and combating antibacterial resistance. Stakeholders, including seafood industry players, regulatory agencies, and healthcare professionals, are essential to ensure effective risk mitigation and safeguard public health in the context of seafood consumption.

BACKGROUND: Although many backcountry first aid kits contain antibiotic ointment, the supply can be quickly exhausted if a patient has extensive wounds or if there are multiple patients.
METHODS: We assessed the antibacterial properties of bark extract from four North American woody plant species known to native Missourians as medicinal plants (Quercus macrocarpa, Salix humilis, Pinus echinata, and Hamamelis vernalis). We tested their antimicrobial properties, with the disc diffusion technique, against four common pathogenic bacterial species: Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterobacter aerogenes (now known as Klebsiella aerogenes).
RESULTS: We report evidence of antibacterial activity of bark extract from all four plant species.
CONCLUSIONS: Our results confirm that traditional uses of these species may be useful in fighting infection and could be especially useful in a wilderness setting when modern antibiotics are exhausted.

Helicobacter pylori (H. pylori) is a strict microaerophilic bacterial species that exists in the stomach, and H. pylori infection is one of the most common chronic bacterial infections affecting humans. Eradicating H. pylori is the preferred method for the long-term prevention of complications such as chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. However, first-line treatment with triple therapy and quadruple therapy has been unable to cope with increasing antibacterial resistance. To provide an updated review of H. pylori infections and antibacterial resistance, as well as related treatment options, we searched PubMed for articles published until March 2024. The key search terms were \"H. pylori\", \"H. pylori infection\", \"H. pylori diseases\", \"H. pylori eradication\", and \"H. pylori antibacterial resistance.\" Despite the use of antimicrobial agents, the annual decline in the eradication rate of H. pylori continues. Emerging eradication therapies, such as the development of the new strong acid blocker vonoprazan, probiotic adjuvant therapy, and H. pylori vaccine therapy, are exciting. However, the effectiveness of these treatments needs to be further evaluated. It is worth mentioning that the idea of altering the oxygen environment in gastric juice for H. pylori to not be able to survive is a hot topic that should be considered in new eradication plans. Various strategies for eradicating H. pylori, including antibacterials, vaccines, probiotics, and biomaterials, are continuously evolving. A novel approach involving the alteration of the oxygen concentration within the growth environment of H. pylori has emerged as a promising eradication strategy.

Diarrhoea remains an important public health concern, particularly in developing countries, and has become difficult to treat because of antibacterial resistance. The development of synergistic antimicrobial agents appears to be a promising alternative treatment against diarrhoeic infections. In this study, the combined effect of tetracycline together with either nitroxoline, sanguinarine, or zinc pyrithione (representing various classes of plant-based compounds) was evaluated in vitro against selected diarrhoeic bacteria (Enterococcus faecalis, Escherichia coli, Listeria monocytogenes, Shigella flexneri, Vibrio parahaemolyticus, and Yersinia enterocolitica). The chequerboard method in 96-well microtiter plates was used to determine the sum of the fractional inhibitory concentration indices (FICIs). Three independent experiments were performed per combination, each in triplicate. It was observed that the combination of tetracycline with either nitroxoline, sanguinarine, or zinc pyrithione produced synergistic effects against most of the pathogenic bacteria tested, with FICI values ranging from 0.086 to 0.5. Tetracycline-nitroxoline combinations produced the greatest synergistic action against S. flexneri at a FICI value of 0.086. The combinations of the agents tested in this study can thus be used for the development of new anti-diarrhoeic medications. However, studies focusing on their in vivo anti-diarrhoeic activity and safety are required before any consideration for utilization in human medicine.

There are still no linear antimicrobial peptides (AMPs) available as a treatment option against bacterial infections. This is caused by several drawbacks that come with AMPs such as limited proteolytic stability and low selectivity against human cells. In this work, we screened a small library of rationally designed new peptides based on the cell-penetrating peptide sC18* toward their antimicrobial activity. We identified several effective novel AMPs and chose one out of this group to further increase its potency. Therefore, we introduced a triazole bridge at different positions to provide a preformed helical structure, assuming that this modification would improve (i) proteolytic stability and (ii) membrane activity. Indeed, placing the triazole bridge within the hydrophilic part of the linear analogue highly increased membrane activity as well as stability against enzymatic digestion. The new peptides, 8A and 8B, demonstrated high activity against several bacterial species tested including pathogenic N. gonorrhoeae and methicillin-resistant S. aureus. Since they exhibited significantly good tolerability against human fibroblast and blood cells, these novel peptides offer true alternatives for future clinical applications and are worth studying in more detail.

In recent years, several threatening developments regarding antibacterial drugs, such as rising bacterial resistance and delivery bottlenecks, have occurred. Since antibacterial drugs are crucial for modern medicine, understanding events and influencing factors relevant for long-term developments is essential. Therefore, we analyzed the number of prescriptions and costs, defined daily dose (DDD) and DDD costs of antibacterial drugs in Germany, based on the Arzneiverordnungsreport (AVR, Drug description report) between 1985 and 2022. Based on prescription rates in 2022, we selected the TOP15 and TOP5. For a more in-depth analysis, we analyzed data from the wissenschaftliches Institut der AOK (WidO, scientific institute of the AOK). The number of prescriptions increased between 1985 and 2013, but since 2014, there has been a declining trend with a noticeable COVID-related dip. Over the years, a shift in drug classes occurred. Once very popular drugs like penicillins and tetracyclines are no longer as important. Conversely, aminopenicillins and cephalosporins have become more relevant. Particularly, the TOP5 drugs have seen an increasing proportion. DDD costs have decreased in most substance classes over time. There is a strong association between decreasing costs and rising prescriptions. Falling costs have a stronger immediate impact on prescriptions that rising costs. When costs are very low, drugs might be prescribed excessively. Supply bottlenecks can also result. The main prescribers are mainly in primary care. Their share of prescription has changed little over the years, but is decreasing regarding total consumption. In comparison to other European countries, Germany ranks in the lower third regarding prescriptions. In most countries, the COVID pandemic has led to a reduced prescription of antibacterial drugs. In conclusion, we provided a comprehensive overview of the antibacterial drug market in Germany over the past four decades and identified costs as a major driver of antibacterial drug prescriptions. Increased costs may reduce uncritical prescription of antibacterial drugs, development of bacterial resistance, supply shortages and occurrence of adverse effects.

Carbon dots (CDs) are novel carbon-based nanomaterials that have been used as photosensitizer-mediated photodynamic therapy (PDT) in recent years due to their good photosensitizing activity. Photosensitizers (PSs) are main components of PDT that can produce large amounts of reactive oxygen species (ROS) when stimulated by light source, which have the advantages of low drug resistance and high therapeutic efficiency. CDs can generate ROS efficiently under irradiation and therefore have been extensively studied in disease local phototherapy. In tumor therapy, CDs can be used as PSs or PS carriers to participate in PDT and play an extremely important role. In bacterial infectious diseases, CDs exhibit high bactericidal activity as CDs are effective in disrupting bacterial cell membranes leading to bacterial death upon photoactivation. We focus on recent advances in the therapy of cancer and bacteria with CDs, and also briefly summarize the mechanisms and requirements for PSs in PDT of cancer, bacteria and other diseases. We also discuss the role CDs play in combination therapy and the potential for future applications against other pathogens.

OBJECTIVE: Antibiotic resistance (ABR) is a major threat to public health. Hospital healthcare professionals are important stakeholders in curbing ABR. To be able to encourage healthcare professionals to act against ABR, information on their perceptions is needed. Yet, summary evidence on how healthcare professionals perceive ABR causes, consequences, and solutions is outdated. This review aims to elucidate these perceptions.
METHODS: We searched MEDLINE, EMBASE, PsycINFO, and CINAHL for literature published until July 6th, 2022, and used Web of Science and Scopus to identify reports citing included studies. Reports of quantitative original research from high-income countries were included if they investigated hospital healthcare professionals\' perceptions about ABR. Descriptive data and data on perceptions about causes, consequences, and solutions regarding ABR were extracted. PROSPERO registration: CRD42022359249.
RESULTS: The database search and citation tracking yielded 13,551 and 694 papers respectively. Forty-eight reports from 46 studies were included in the review. These studies were performed between 1999 and 2023 and included between 8 and 1362 participants. Healthcare professionals perceived ABR as a problem that is more severe nationally than locally and they primarily recognize ABR as a distant and abstract problem. Studies mostly concurred on prescribing behavior as a cause and a solution for ABR, while external causes and solutions (e.g., in agriculture) elicited less agreement.
CONCLUSIONS: Studies with a primary focus on the perceptions of healthcare professionals about ABR are limited. Healthcare professionals perceive prescribing behavior as a major cause of ABR and a focus area for ABR solutions.

Infectious diseases are a significant challenge to global healthcare, especially in the face of increasing antibiotic resistance. This urgent issue requires the continuous exploration and development of new antimicrobial drugs. In this regard, the secondary metabolites derived from endophytic microorganisms stand out as promising sources for finding antimicrobials. Endophytic microorganisms, residing within the internal tissues of plants, have demonstrated the capacity to produce diverse bioactive compounds with substantial pharmacological potential. Therefore, numerous new antimicrobial compounds have been isolated from endophytes, particularly from endophytic fungi and actinomycetes. However, only a limited number of these compounds have been subjected to comprehensive studies regarding their mechanisms of action against bacterial cells. Furthermore, the investigation of their effects on antibiotic-resistant bacteria and the identification of biosynthetic gene clusters responsible for synthesizing these secondary metabolites have been conducted for only a subset of these promising compounds. Through a comprehensive analysis of current research findings, this review describes the mechanisms of action of antimicrobial drugs and secondary metabolites isolated from endophytes, antibacterial activities of the natural compounds derived from endophytes against antibiotic-resistant bacteria, and biosynthetic gene clusters of endophytic fungi responsible for the synthesis of bioactive secondary metabolites.