Introduction:
A recent study was published in the journal Molecular Cell in September 2022; Scientists at McMaster University have identified a toxin that bacteria use to kill other bacteria through bacterial competition within the microbiome by a new mechanism targeting RNA molecules, thus disrupting the various vital functions resulting from it.
Among the group of proteins that the team tested is a protein called RhsP2 produced by "Pseudomonas aeruginosa"; this works by directly affecting RNA molecules with two proposed mechanisms:
1/ ADP ribosylation to prevents the binding of amino acids and then synthesis of bacterial proteins necessary for life.
2/ Inactivation of ribonuclease RNase P.

Work methodology:
Using computational docking and modeling, the interactions between two proteins, namely RhsP2toxin/16S rRNA target, were investigated in detail in order to identify residues belonging to the active sites of the studied toxin RhsP2, which targets 16S rRNA. In our study, we relied on different docking programs such as AuotoDock VINA, HADDOCK lite server, and HADDOCK 2.4 server, and compared the results with a reference compound, rifamycin (which works with a mechanism similar to our studied compound), based on criteria related to affinity binding energy and regularity of atoms within the pocket (RMSD).

Conclusions:
The results show that the HADDOCK lite server showed the closest model (DRUD2) to rifamycin in interaction with the active pocket of the target protein 16S rRNA, followed by the HADDOCK 2.4 (DRUG3). and finally the model generated by the Structuring AuotoDock VINA method (DRUG1).
* Our results were reasonable as a preliminary prediction with one target 16S rRNA, and we can say that the toxic substance RhsP2 has a good interaction with 16S rRNA so we propose it as an inhibitor by binding to the active pocket (such as the action of rifamycin) and inhibiting its function in translating amino acids into proteins.

Biofilms composed of foodborne bacterial pathogens pose a significant challenge to food safety, as they enhance the microbial persistence in processing environments. Quorum sensing (QS), particularly the autoinducer-2 (AI-2) signaling system, which is widely conserved among both Gram-positive and Gram-negative bacteria and is involved in both intra- and inter-species bacterial communication, is employed to regulate group behaviors based on cell density and plays a crucial role in biofilm formation by pathogens such as Listeria monocytogenes and Staphylococcus aureus. Lactic acid bacteria (LAB) have been used for centuries in food fermentation to improve the sensory and nutritional profiles and preserve against detrimental microflora. The use of LAB and/or their metabolites as natural quorum-sensing inhibitors (QSIs) may represent a promising, eco-friendly antibiofilm strategy. This study investigates the ability of LAB-derived cell-free supernatants (CFSs) to interfere with AI-2-mediated QS and inhibit biofilm formation in monocultures of L. monocytogenes and S. aureus. To achieve this, a collection of 89 foodborne LAB isolates was initially screened for either AI-2 production or inhibition using Vibrio harveyi luminescence assays. Twenty CFSs displaying AI-2 interference activity were then selected and further evaluated for their antibiofilm potential at sub-minimum inhibitory concentrations (sub-MICs) using microtiter plate biofilm assays based on crystal violet staining. The results revealed that 61.8% (55/89) of the tested CFSs contained AI-2-like signals, while 28.1% (25/89) demonstrated significant AI-2-QSI activity. Almost all of the tested CFSs exhibiting AI-2 QS interference, except for one, significantly limited L. monocytogenes biofilm formation, while one of them also reduced the biomass accumulation of S. aureus biofilms significantly (by 47.8%). These findings highlight the potential of crude LAB extracts to disrupt QS and serve as novel antibiofilm agents in food safety applications. Further research will examine their efficacy against multi-species biofilms under food-relevant conditions.

This project was funded by the National Recovery and Resilience Plan Greece 2.0, European Union—NextGenerationEU (HFRI Project 15572).

The increasing incidence of antibiotic resistance among Klebsiella pneumoniae isolates, along with their ability to form biofilms, places this pathogen in the critical priority group for which new antimicrobial treatments are urgently needed. The combination of plant compounds and antibiotics is a promising approach for enhancing antimicrobial activity. The phytochemical 1,8-cineole, which is effective against K. pneumoniae, is a good candidate for the development of novel antibacterial combination therapies. The aim of this study was to evaluate the combined action of 1,8-cineole with ciprofloxacin against K. pneumoniae in both planktonic cultures and biofilms. For this purpose, the planktonic growth (OD_600nm) of a clinical K. pneumoniae strain was quantified after treatment with the individual compounds or their combinations. Based on the obtained data, two types of drug interaction analyses were performed: 1) the fractional inhibitory concentration index (FICI) was calculated after determining the minimum inhibitory concentrations and 2) the BLISS model in the Combenefit software was used. A synergistic effect of 1,8-cineole with ciprofloxacin was revealed based on both analyses. In addition, the minimum bactericidal concentrations (MBCs) were determined by means of colony-forming unit (CFU) counting. The anti-biofilm effects of ciprofloxacin and 1,8-cineole, either alone or in combination, were assessed on pre-formed (24 h old) K. pneumoniae biofilms. The biomass was measured by means of crystal violet staining, and the cell viability was quantified using CFU counting. The most effective combined treatment was obtained using five-times ciprofloxacin MBC and half the 1,8-cineole MBC, resulting in a 90% biomass decrease and 4 Log₁₀ reduction in cell viability. In contrast, these anti-biofilm effects were not observed when the same concentrations of the individual compounds were assayed. Taken together, our findings indicate that 1,8-cineole is a promising candidate for combinatorial therapies with clinically relevant antibiotics to treat K. pneumoniae infections.

This study presents the synthesis and characterization of apatite–lignin–aloe vera (Ap/Lig/AV) coatings, utilizing the Matrix-Assisted Pulsed Laser Evaporation (MAPLE) technique. The incorporation of natural and renewable materials, such as lignin and aloe vera extract, offers a safer and more environmentally friendly alternative to conventional synthetic antibiotics. This innovative approach aims to not only provide infection prevention but also to address the growing concern of primary and secondary resistance to existing drugs, which poses a significant public health challenge.

Our findings indicate that the chemical properties and stoichiometry of the synthesized coatings were preserved throughout the process. A uniform and homogeneous distribution of the materials was achieved when the amount of essential oil matched that of the organic components. The coatings exhibited hydrophilic characteristics and enhanced cellular viability in cultures with cancerous Mg 63 cells. Furthermore, the composite materials demonstrated significant antimicrobial activity against Gram-positive and Gram-negative bacteria, including Escherichia coli and Staphylococcus aureus, as well as against the fungus Candida albicans.

The utilization of these naturally derived products not only presents a cost-effective solution but also contributes to the development of biodegradable thin films with antibacterial, antioxidant, and anti-inflammatory properties. These advancements highlight the potential of Ap/Lig/AV coatings in biomedical applications, particularly in the context of reducing reliance on synthetic antibacterial agents.

Today, in Europe and North America, the emergence of non-tuberculous mycobacteria (NTM) infections is now outstripping that of Mycobacterium tuberculosis. NTM are ubiquitous and opportunistic in people with bronchiectasis or chronic respiratory disease. Among the NTM known for their pulmonary pathogenicity, mycobacteria from the Mycobacterium avium complex (MAC) are the most common, responsible for 80% of NTM infections. Current NTM treatments require a combination of antibiotics over a long period and have numerous side effects. For example, the first-line treatment for MAC infections includes a combination of three drugs, namely macrolide, rifamycin and ethambutol, administrated for at least twelve months after sputum conversion. These drugs can cause a number of inconveniences or serious effects, including hepatotoxicity, ocular disorders, etc. In addition, the moderate efficacy of this treatment (52% to 60% success rate) is also compromised by the increasing resistance of NTM to macrolides. Consequently, there is an urgent need to develop safer molecules, ideally with novel mechanisms of action, to limit the risk of antibiotic resistance. The quinoline-based pharmacophore is found in mefloquine (MQ), which targets ATP synthase, a vital enzyme for mycobacteria. However, MQ has a moderate activity against NTM (e.g., MIC = 4 µg/mL on MAC) and it can induce side effects on the central nervous system. To improve the selectivity index (SI), novel amino-alcohol-quinolines (AAQs), designed as analogues of MQ, have been developed. A hit compound was identified on MAC with a SI higher than that of MQ (SI = 5.8 vs 0.4) and it has an additive effect with the three drugs used in first-line treatment against MAC. This study presents the design rationale for AAQs, describes their synthesis, and provides an in vitro biological evaluation, including assessments of antimycobacterial activity, cytotoxicity, and potential synergistic effects.

For decades, antimicrobial resistance has posed a growing threat to the effective treatment of an expanding range of infections caused by bacteria, parasites, viruses, and fungi. This issue disproportionately affects developing countries or those grappling with significant social inequality. In response, medicinal chemistry has developed various drugs that are effective in many cases. However, the improper use of these drugs and the adaptive strategies of prokaryotic cells to evade therapeutic agents have significantly diminished their pharmacological efficacy. To address this challenge, the development of new drugs is essential to improve treatment outcomes in a more efficient, less toxic manner and to overcome the phenomenon of resistance. This research focuses on the synthesis and antibacterial evaluation of novel Schiff base-type compounds derived from benzimidazoles coordinated with group 10 metals (nickel, palladium, platinum), which are well-documented for their antimicrobial and antitumor activities. The synthesized compounds were characterized using spectroscopic and spectrometric techniques, and their antibacterial activity was assessed in vitro against resistant bacteria isolated from the Magdalena region of Colombia, employing the broth microdilution method. The minimum inhibitory concentration (MIC) values ​​ranged between 250-0.5 μg/mL against resistant strains of gram-positive (S. aureus) and gram-negative (E. coli, K. pneumoniae) bacteria. Results indicate a synergistic effect between the metal center and the organic ligand, enhancing the biological activity. Notably, platinum-based complexes emerged as promising candidates , even presenting MIC up to 0.5 μg/mL, similar to ciprofloxacin used as a control drug for S. aureus.

As per the WHO’s “Bacterial Priority Pathogen List”, Carbapenem-resistant A. baumannii (CRAB) is categorized as belonging to the critical priority pathogen group due to the extreme paucity of treatment options (1). A. baumannii causes several nosocomial infections such as pneumonia, sepsis and bacteraemia; skin and soft tissue infections; and meningitis (2). To respond to the urgent and unmet need of identifying novel antibiotics that are active against CRAB, we designed, synthesized and tested 29 naphthalimide derivatives by incorporating the hydrazine group against CRAB BAA-1605. From these compounds, 5b, 5c, 5d and 5e exhibited MICs ranging between 0.5 and 1 μg/ml, and all compounds except 5e displayed >200 selectivity indeces (SIs) against Vero cells. Compound 5d was chosen as a representative and tested against an MDR clinical strain panel, with strains that are resistant to meropenem, levofloxacin and minocycline. In these tests, 5d displayed equi-potent activity. In addition, 5d demonstrated synergy with tobramycin, and the synergy was confirmed by means of a combination time kill assay against CRAB BAA-1605. From the above data, 5d exhibits promise as a potential antibacterial scaffold against CRAB (3).

References:

1. https://iris.who.int/bitstream/handle/10665/376776/9789240093461-eng.pdf?sequence=1
2. Sieniawski, K., Kaczka, K., Rucinska, M., Gagis, L., & Pomorski, L. (2013). Acinetobacter baumannii nosocomial infections. Polski Przeglad Chirurgiczny/ Polish Journal of Surgery, 85(9), 483–490. https://doi.org/10.2478/pjs-2013-0075
3. https://doi.org/10.1039/D4MD00368C

^{Introduction: Abacha, a traditional African salad made from processed cassava, is widely consumed in southeastern Nigeria, including Ebonyi State. Its preparation often involves exposure to open air, inadequate hygiene, and unregulated water sources, making it susceptible to bacterial contamination and foodborne illnesses. This study examines the antibiotic susceptibility of bacteria isolated from Abacha sold at Ebonyi State University (EBSU) and Alex-Ekwueme Federal University, Ndufu-Alike, Ikwo (FUNAI).}

^{Methods: Samples were collected from six vendors on both university campuses. Standard microbiological techniques were used for bacterial isolation and confirmation, while the disc diffusion method was applied for antibiotic susceptibility testing.}

^{Results: All six Abacha samples showed microbial contamination, with the highest levels found at the FUNAI front gate and the lowest levels found at EBSU Presco campus. Total bacterial and coliform counts exceeded tolerable limits, with counts above 10⁴ (total viable count) and 10¹ (total coliform count). Identified bacteria included Staphylococcus aureus (20.0%), Pseudomonas aeruginosa (16.7%), and others. High resistance was observed against erythromycin, cefotaxime, and ampicillin (up to 80%).}

^{Conclusion: Ciprofloxacin (96.7%), colistin, and gentamycin showed the highest efficacy, likely due to their broad spectrum and lower resistance rates. These findings highlight the need for improved hygiene among street food vendors to reduce bacterial contamination and antibiotic resistance risks.}

Background:

Antimicrobial resistance is a critical global concern, impacting patient outcomes and healthcare costs. This study evaluates antibiogram data and resistance patterns among various sample cultures from a tertiary care center in India.

Methods:

A prospective cross-sectional study was conducted for the period of 2023 to 2025. Bacterial isolates from urine, blood, respiratory, and exudate cultures were identified using biochemical tests. The Kirby–Bauer disc diffusion method, which was recommended by CLSI's 2023 guidelines, was used to test for antibiotic susceptibility. The resistance patterns were analyzed for MRSA, ESBL, carbapenems, vancomycin, linezolid, tigecycline, and colistin. To look at the trends in resistance, antibiogram data were grouped for Gram-negative (E. coli, Klebsiella, Pseudomonas, Enterobacter, Morganella, Acinetobacter, and Proteus) and Gram-positive pathogens (Enterococcus, Staphylococcus, and CONS).

Results:

Among the Gram-negative bacteria, ESBL-producing E. coli (56%) and Klebsiella pneumoniae (62%) were predominant in the urine cultures, with K. pneumoniae showing 24% carbapenem resistance. The blood cultures showed that K. pneumoniae was resistant to 56% ESBL and 40% carbapenem. On the other hand, the respiratory cultures showed that Enterobacter spp. were resistant to ESBL the most (93.4%). The exudate cultures showed E. coli (75%) and K. pneumoniae (56%) with significant ESBL resistance. Among the Gram-positive bacteria, MRSA was found in 35.3% of blood infections and 27.3% of respiratory cultures. MRCONS exhibited 53.58% resistance in the blood, and VRE was detected in 9.1% of bloodstream infections. The antibiogram data showed that E. coli was highly susceptible to amikacin (93%) and imipenem (94%) in the urine, and Pseudomonas spp. were still highly susceptible to polymyxin B (100%) but not to ceftazidime (88%).

Conclusions:

This study shows that antimicrobial resistance is rising at an alarming rate, especially in bloodstream infections caused by ESBL-producing E. coli and K. pneumoniae, carbapenem-resistant Acinetobacter spp., and MRSA. These findings emphasize the need for stringent antibiotic stewardship to mitigate resistance spread, especially in developing countries.

The antibiotic resistance crisis has been a global health threat for decades, because bacterial pathogens, viruses, and other parasites evolve to resist current antibiotics. This has led to unmet needs for the discovery of new compounds that are different from the current antimicrobials. Antimicrobial peptides (AMPs), as promising alternatives to conventional antibiotics, have attracted growing interest owing to their lower likelihood of causing bacteria to develop resistance compared with antibiotics. In this study, we rationally designed a series of peptides, evaluated their antibacterial activities, and investigated their modes of action against bacteria.

Bacterial initiation factor 1 (IF1) is a small protein but plays a critical role in regulating bacterial protein biosynthesis. According to our structural studies on IF1 proteins from three representative bacterial pathogens—Pseudomonas aeruginosa, Clostridioides difficile, and Helicobacter pylori—and their interactions with the 30S ribosomal subunits, we designed a series of IF1-derived short peptides. These peptides were tested for inhibitory activities against various bacteria, including Gram-positive and Gram-negative strains. The results showed that the MIC (minimum inhibitory concentration) of IF1-peptides is as low as 20 uM against P. aeruginosa ATCC 47085, 60 uM against C. difficile ATCC 43593, and 18 uM against Staphylococcus epidermitis ATCC 12228 and Bacillus cereus ATCC 14579. Further investigation of the mode of action showed that IF1-derived peptides did not affect the bacterial membrane integrity based on the SEM results; however, they displayed dose-dependent inhibition against bacterial protein synthesis. These results suggest IF1-derived peptides as new type of antibacterial candidate. Since bacterial IF1 is a highly conserved element of the prokaryotic translational apparatus, these results provide a potential avenue for the rational design of new antimicrobials.