Helicobacter pylori (H. pylori), classified as a Group 1 carcinogen by the International Agency for Research on Cancer (IARC), is linked to gastric cancer. The progression from atrophy to metaplasia, dysplasia, and carcinoma constitutes the pathway for intestinal-type gastric carcinoma development. H. pylori infection significantly increases gastric cancer risk, particularly in individuals with atrophic gastritis. Virulence factors like CagA and VacA disrupt host signaling pathways, contributing to chronic inflammation and carcinogenesis. Pro-inflammatory cytokines and dysregulated tumor suppressor genes further fuel this process. Eradicating H. pylori reduces gastric cancer incidence, especially in patients with atrophic gastritis and/or intestinal metaplasia. However, it may not prevent cancer in those with advanced pre-neoplastic lesions. Early detection and management of H. pylori infection are crucial in mitigating gastric cancer risk, offering significant benefits.

Carbapenemase-producing gram-negative bacteria (CP-GNB) infections threaten public health with high mortality, morbidity and treatment costs. Although frequencies remain low in Australia (total number of CP-GNB infections reported was 907 in 2022), blaIMP-4 has established low levels of endemicity in many states. Imipenemase metallo-β-lactamase types alone accounted for more than half of all carbapenemases in carbapenemase-producing Enterobacterales isolates in Australia, particularly in Enterobacter cloacae complex. New Delhi metallo-β-lactamase constitutes almost 25% of all carbapenemases in Australia and was identified predominantly in Escherichia coli. The OXA-48-like carbapenemases include almost 10% of all carbapenemases and are mainly seen in Klebsiella pneumoniae and E. coli. Although K. pneumoniae carbapenemase-type carbapenemases are rare in Australia, some local outbreaks have occurred. Most carbapenem-resistant (CR) Pseudomonas aeruginosa strains in Australia do not produce carbapenemases. Finally, OXA-23-like carbapenemases are overwhelmingly positive in CR-Acinetobacter baumannii strains in Australia. Treatment of CR-GNB infections challenges physicians. Of 10 new antibiotics active against at least some CR-GNB infections that are approved by the US Food and Drug Administration, just three are approved for use in Australia. In this context, there is still an unmet need for novel antibacterials that can be used for the treatment of CR-GNB infections in Australia, as well as a pressing requirement for new mechanisms to \'de-link\' antibiotic sales from their availability. In this narrative review, we aim to overview the epidemiology and clinical significance of carbapenem resistance in Australia as it pertains to Enterobacterales, P. aeruginosa and A. baumannii.

The objective of this meta-analysis is to delineate the association between H. pylori CagA serological status and the prevalence of gastric precancerous lesions (GPL). We searched peer-reviewed articles up to October 2023. The extraction of data from the included studies was carried out as well as the quality assessment. Pooled effect sizes were calculated using a random effect model. Thirteen studies met the inclusion criteria, comprising 2728 patients with GPL and 17 612 controls. The aggregate odds ratio (OR) for the association between serum CagA and GPL was 2.74 (95% CI = 2.25-3.32; P  = 0.00; I 2  = 60.4%), irrespective of H. pylori infection status. Within the H. pylori -infected cohort, the OR was 2.25 (95% CI = 1.99-2.56; P  = 0.00; I 2  = 0.0%). Conversely, among the non-infected individuals, the OR was 1.63 (95% CI = 1.04-2.54; P  = 0.038; I 2  = 0.0%). Heterogeneity was explored using subgroup and meta-regression analyses, indicating that the variability between studies likely stemmed from differences in disease classification. Our results demonstrated robustness and negligible publication bias. The meta-analysis underscores a more pronounced association between H. pylori CagA seropositivity and the risk of developing GPL than between seronegativity and the same risk, irrespective of H. pylori infection status at the time. Additionally, the strength of the association was heightened in the presence of an active H. pylori infection. The implications of these findings advocate for the utility of CagA serostatus as a potential biomarker for screening GPL.

Carbapenems are effective drugs against bacterial pathogens and resistance to them is considered a great public health threat, especially in notorious nosocomial pathogens like Acinetobacter baumannii and Pseudomonas aeruginosa. In this study, we aimed to determine the prevalence of carbapenem resistance in A. baumannii and P. aeruginosa infections in Sub-Saharan Africa. Databases (PubMed, Scopus, Web of Science, and African Journal Online) were systematically searched following the Preferred Reporting Items for Systematic review and meta-analysis protocols (PRISMA-P) 2020 statements for articles reporting carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) prevalence between 2012 and 2022. Pooled prevalence was determined with the random effect model and funnel plots were used to determine heterogeneity in R. A total of 47 articles were scanned for eligibility, among which 25 (14 for carbapenem-resistant A. baumannii and 11 for carbapenem-resistant P. aeruginosa) were included in the study after fulfilling the eligibility criteria. The pooled prevalence of CRPA in the present study was estimated at 8% (95% CI; 0.02-0.17; I2 = 98%; P <0.01). There was high heterogeneity (Q = 591.71, I2 = 98.9%; P<0.0001). In addition, this study\'s pooled prevalence of CRAB was estimated at 20% (95% CI; 0.04-0.43; I2 = 99%; P <0.01). There was high heterogeneity (Q = 1452.57, I2 = 99%; P<0.0001). Also, a funnel plot analysis of the studies showed high degree of heterogeneity. The carbapenemase genes commonly isolated from A. baumannii in this study include blaOXA23, blaOXA48, blaGES., blaNDM, blaVIM, blaOXA24, blaOXA58, blaOXA51, blaSIM-1, blaOXA40, blaOXA66, blaOXA69, blaOXA91, with blaOXA23 and blaVIM being the most common. On the other hand, blaNDM, blaVIM, blaIMP, blaOXA48, blaOXA51, blaSIM-1, blaOXA181, blaKPC, blaOXA23, blaOXA50 were the commonly isolated carbapenemase genes in P. aeruginosa, among which blaVIM and blaNDM genes were the most frequently isolated. Surveillance of drug-resistant pathogens in Sub-Saharan Africa is essential in reducing the region\'s disease burden. This study has shown that the region has significantly high multidrug-resistant pathogen prevalence. This is a wake-up call for policymakers to put in place measures to reduce the spread of these critical priority pathogens.

Virulent Rhodococcus equi strains expressing virulence-associated 15-17 kDa protein (VapA) and having a large virulence plasmid (pVAPA) of 85-90 kb containing vapA gene are pathogenic for horses. In the last two decades, following pVAPA, two host-associated virulence plasmid types of R. equi have been discovered: a circular plasmid, pVAPB, associated with porcine isolates in 1995, and a recently detected linear plasmid, pVAPN, related to bovine and caprine isolates. Molecular epidemiological studies of R. equi infection in foals on horse-breeding farms in Japan and many countries around the world have been conducted in the last three decades, and the epidemiological studies using restriction enzyme digestion patterns of plasmid DNAs from virulent isolates have shown 14 distinct pVAPA subtypes and their geographical preference. This short review summarizes previous reports regarding equine-associated pVAPA subtypes in the world and discusses their geographic distribution from the standpoint of horse movements.

Pseudomonas aeruginosa, an increasingly common competitive and biofilm organism in healthcare infection with sophisticated, interlinked and hierarchic quorum systems (Las, Rhl, PQS, and IQS), creates the greatest threats to the medical industry and has rendered prevailing chemotherapy medications ineffective. The rise of multidrug resistance has evolved into a concerning and potentially fatal occurrence for human life. P. aeruginosa biofilm development is assisted by exopolysaccharides, extracellular DNA, proteins, macromolecules, cellular signaling and interaction. Quorum sensing is a communication process between cells that involves autonomous inducers and regulators. Quorum-induced infectious agent biofilms and the synthesis of virulence factors have increased disease transmission, medication resistance, infection episodes, hospitalizations and mortality. Hence, quorum sensing may be a potential therapeutical target for bacterial illness, and developing quorum inhibitors as an anti-virulent tool could be a promising treatment strategy for existing antibiotics. Quorum quenching is a prevalent technique for treating infections caused by microbes because it diminishes microbial pathogenesis and increases microbe biofilm sensitivity to antibiotics, making it a potential candidate for drug development. This paper examines P. aeruginosa quorum sensing, the hierarchy of quorum sensing mechanism, quorum sensing inhibition and quorum sensing inhibitory agents as a drug development strategy to supplement traditional antibiotic strategies.

The delivery of Helicobacter pylori CagA into host cells was long believed to occur through the integrin cell surface receptors. However, the role of CEACAM receptors has recently been highlighted, instead. Here, we have categorized the existing experimental evidence according to whether deletion, upregulation, downregulation, or inhibition of the target ligands (T4SS or HopQ) or receptors (integrins or CEACAMs), result in alterations in CagA phosphorylation, cell elongation, or IL-8 production. According to our analysis, the statistics favor the essence of most of the T4SS constituents and the involvement of HopQ adhesin in all three functions. Concerning the integrin family, the collected data is controversial, but yielding towards it being dispensable or involved in CagA translocation. Yet, regarding cell elongation, more events are showing β1 integrin being involved, than αvβ4 being inhibitory. Concerning IL-8 secretion, again there are more events showing α5, β1 and β6 integrins to be involved, than those showing inhibitory roles for β1, β4 and β6 integrins. Finally, CEACAM 1, 3, and 5 are identified as mostly essential or involved in CagA phosphorylation, whereasCEACAM 4, 7, and 8 are found dispensable and CEACAM6 is under debate. Conversely, CEACAM1, 5 and 6 appear mostly dispensable for cell elongation. Noteworthy is the choice of cell type, bacterial strain, multiplicity and duration of infection, as well as the sensitivity of the detection methods, all of which can affect the variably obtained results.

Salmonella, a Gram-negative bacterium that infects humans and animals, causes diseases ranging from gastroenteritis to severe systemic infections. Here, we discuss various strategies used by Salmonella against host cell defenses. Epithelial cell invasion largely depends on a Salmonella pathogenicity island (SPI)-1-encoded type 3 secretion system, a molecular syringe for injecting effector proteins directly into host cells. The internalization of Salmonella into macrophages is primarily driven by phagocytosis. After entering the host cell cytoplasm, Salmonella releases many effectors to achieve intracellular survival and replication using several secretion systems, primarily an SPI-2-encoded type 3 secretion system. Salmonella-containing vacuoles protect Salmonella from contacting bactericidal substances in epithelial cells and macrophages. Salmonella modulates the immunity, metabolism, cell cycle, and viability of host cells to expand its survival in the host, and the intracellular environment of Salmonella-infected cells promotes its virulence. This review provides insights into how Salmonella subverts host cell defenses for survival.

Staphylococcus aureus is a common human pathogen. Methicillin-resistant Staphylococcus aureus (MRSA) infections pose significant and challenging therapeutic difficulties. MRSA often acquires the non-native gene PBP2a, which results in reduced susceptibility to β-lactam antibiotics, thus conferring resistance. PBP2a has a lower affinity for methicillin, allowing bacteria to maintain peptidoglycan biosynthesis, a core component of the bacterial cell wall. Consequently, even in the presence of methicillin or other antibiotics, bacteria can develop resistance. Due to genes responsible for resistance, S. aureus becomes MRSA. The fundamental premise of this resistance mechanism is well-understood. Given the therapeutic concerns posed by resistant microorganisms, there is a legitimate demand for novel antibiotics. This review primarily focuses on PBP2a scaffolds and the various screening approaches used to identify PBP2a inhibitors. The following classes of compounds and their biological activities are discussed: Penicillin, Cephalosporins, Pyrazole-Benzimidazole-based derivatives, Oxadiazole-containing derivatives, non-β-lactam allosteric inhibitors, 4-(3H)-Quinazolinones, Pyrrolylated chalcone, Bis-2-Oxoazetidinyl macrocycles (β-lactam antibiotics with 1,3-Bridges), Macrocycle-embedded β-lactams as novel inhibitors, Pyridine-Coupled Pyrimidinones, novel Naphthalimide corbelled aminothiazoximes, non-covalent inhibitors, Investigational-β-lactam antibiotics, Carbapenem, novel Benzoxazole derivatives, Pyrazolylpyridine analogues, and other miscellaneous classes of scaffolds for PBP2a. Additionally, we discuss the penicillin-binding protein, a crucial target in the MRSA cell wall. Various aspects of PBP2a, bacterial cell walls, peptidoglycans, different crystal structures of PBP2a, synthetic routes for PBP2a inhibitors, and future perspectives on MRSA inhibitors are also explored.

BACKGROUND: Acinetobacter baumannii produce biofilm and efflux pumps. This systematic review study aimed to provide new strategies to inhibit the efflux pumps and biofilm in A. baumannii using nanoparticles.
METHODS: In this research, analyses from 2000 to February 24, 2022, were performed by the Statement of Preferred Reporting Items for Systematic Reviews (PRISMA). Keywords include Acinetobacter baumannii (A. baumannii) AND (biofilm) AND (anti-biofilm activity) AND (nanoparticles) AND (solid lipid NPS) AND (lipid nanocarriers), and in other searches include Acinetobacter baumannii (A. baumanni) AND (efflux pumps) AND (nanoparticles) AND (solid lipid NPS) AND (lipid nanocarriers). Searches were conducted in English databases, including Science Direct, PubMed, Scopus, Ovid, and Cochrane.
RESULTS: At first, 136 studies were extracted, but after removing duplicates, 116 cases remained for further analysis. After evaluating the title and abstract of each study, 95 unrelated studies were excluded. The remaining 25 studies were reviewed based on full texts. Considering the inclusion/exclusion criteria, 19 studies were selected. In this study, metal nanoparticles were the most used nanoparticles for anti-biofilm and efflux pump purposes, and among these nanoparticles, silver nanoparticles (AgNPs) contributed the most.
CONCLUSIONS: The present study shows that nanoparticles have potential and significant effects in inhibiting biofilm and efflux pumps in A. baumannii isolates, which researchers can consider in light of the increasing prevalence of antibiotic resistance.