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Antibacterial Activity against Drug-Resistant Strains, 2nd Edition
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Antibacterial Activity against Drug-Resistant Strains, 2nd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: 20 July 2025 | Viewed by 3606

Special Issue Editors

Dr. Rosa Sessa

E-Mail Website
Guest Editor
Department of Public Health and Infectious Diseases, University of Rome “Sapienza”, 00185 Rome, Italy
Interests: Chlamydia; host defence factors; genital infection;pathogenesis of male infertility; Chlamydia-host cell interaction; new anti-Chlamydial drugs; chronic inflammatory diseases
Special Issues, Collections and Topics in MDPI journals
Dr. Simone Filardo

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Guest Editor
Department of Public Health and Infectious Diseases, “Sapienza” University, 00185 Rome, Italy
Interests: human microbiota; bioinformatic analysis; host-pathogen interactions; identification of novel antimicrobial molecules; study of C. trachomatis pathogenesis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Antibacterial resistance is one of the greatest threats to human health, resulting in an increased number of deaths due to once curable infectious diseases. Indeed, the emergence of drug-resistant bacteria has been prioritized by the World Health Organization as one of the top ten public health problems worldwide. Over the years, the widespread misuse and overuse of antibiotics in the human, animal, and environmental domains have led to the global rapid spread of multi-drug resistant pathogens, beginning with the emergence of methicillin-resistant Staphylococcus aureus. The following appearance of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae all over the globe, including some Escherichia coli strains and the ESKAPE pathogens, has further limited the treatment options at our disposal. In addition, other emerging bacterial pathogens, like intracellular bacteria, are acquiring increasing resistance to standard treatments, hence the need for novel molecules. The aim of this Special Issue is to encourage original articles tackling this current issue, including the antibacterial activity of novel compounds as well as the molecular mechanisms underlying the antibiotic resistance for the discovery of new promising targets.

Dr. Rosa Sessa
Dr. Simone Filardo
Guest Editors

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Keywords

  • antibacterial activity
  • novel antimicrobial agents
  • drug-resistant strains
  • molecular mechanisms
  • emerging drug-resistant pathogens
  • genetic determinants
  • impact of MDR pathogens on human health
  • molecular methods for the diagnosis of antibiotic resistance

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Published Papers (3 papers)

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Research

18 pages, 2023 KiB  
Article
Antimicrobial Activity of a Synthetic Brevibacillin Analog Against Multidrug-Resistant Campylobacter spp.
by Khaled Abdallah, Omar Fliss, Nguyen Phuong Pham, Louis David Guay, Hélène Gingras, Chantal Godin, Philippe Leprohon, Eric Biron, Ismail Fliss and Marc Ouellette
Int. J. Mol. Sci. 2025, 26(10), 4657; https://doi.org/10.3390/ijms26104657 - 13 May 2025
Viewed by 320
Abstract
Campylobacter spp. is one of the most prevalent causes of zoonotic foodborne infections associated with diarrhea in humans. The growing threat of antibiotic resistance calls for innovative approaches. The antimicrobial lipopeptide brevibacillin produced by Brevibacillus laterosporus and its synthetic analog brevibacillin Thr1 showed [...] Read more.
Campylobacter spp. is one of the most prevalent causes of zoonotic foodborne infections associated with diarrhea in humans. The growing threat of antibiotic resistance calls for innovative approaches. The antimicrobial lipopeptide brevibacillin produced by Brevibacillus laterosporus and its synthetic analog brevibacillin Thr1 showed promising activity against Salmonella and E. coli. The latter is a 1602.13 Da positively charged (+3) synthetic peptide of 13 residues that showed reduced cytotoxicity (IC50 of 32.2 µg/mL against Caco-2 cells) and hemolytic activity (1.2% hemolysis at 128 µg/mL) compared to the native peptide. It contains an N-terminal L-isoleucic fatty acid chain and four non-proteinogenic amino acids and ends with valinol at its C-terminus. One key structural modification is the substitution of α,β-dehydrobutyric acid with threonine. We investigated the antimicrobial potential of the synthetic brevibacillin Thr1 analog against a collection of 44 clinical Campylobacter spp. that were obtained from two reference laboratories. Susceptibility testing revealed marked resistance to ciprofloxacin, tetracycline, and ampicillin among the strains, with more than half expressing a multidrug-resistant phenotype. The genomes of the 44 strains were sequenced to study the genes responsible for their antimicrobial resistance. Tetracycline resistance was associated with tet(O), ciprofloxacin resistance with mutations in gyrA and regulatory sequences modulating the expression of an efflux system, and aminoglycoside resistance with genes of the aph family. The brevibacillin Thr1 analog was produced by chemical synthesis, and evaluation of its activity against a subset of clinical strains by microdilution revealed minimum inhibitory concentration and minimum bactericidal concentration ranging from 8 µg/mL to 64 µg/mL. The peptide was active against multidrug-resistant isolates with a bactericidal effect. Of note, despite numerous attempts, it proved impossible to select Campylobacter spp. for resistance to the brevibacillin Thr1 analog. These results underline the potential of lipopeptides, notably brevibacillin, as antimicrobial alternatives against antibiotic-resistant Campylobacter bacterial infections. Full article
(This article belongs to the Special Issue Antibacterial Activity against Drug-Resistant Strains, 2nd Edition)
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14 pages, 627 KiB  
Article
Effect of Sub-Inhibitory Concentrations of Quaternary Ammonium Compounds and Heavy Metals on Antibiotic Resistance and Expression of Virulence Factors Among Staphylococcus spp. from Dairy Products
by Zuzanna Byczkowska-Rostkowska, Joanna Gajewska, Anna Zadernowska and Wioleta Chajęcka-Wierzchowska
Int. J. Mol. Sci. 2025, 26(6), 2429; https://doi.org/10.3390/ijms26062429 - 8 Mar 2025
Viewed by 670
Abstract
Antimicrobial resistance is spreading rapidly throughout the world. The food chain can be one of the routes of transmission for microorganisms containing drug-resistance genes and thus serve as a channel for their transmission. Environmental stress and methods of preventing the spread of microorganisms [...] Read more.
Antimicrobial resistance is spreading rapidly throughout the world. The food chain can be one of the routes of transmission for microorganisms containing drug-resistance genes and thus serve as a channel for their transmission. Environmental stress and methods of preventing the spread of microorganisms trigger adaptive responses in bacterial cells. The aim of the present study was to determine the effect of the stress induced by sub-inhibitory concentrations (SICs) of cadmium chloride and benzalkonium chloride on antibiotic resistance and the expression of selected virulence factors in Staphylococcus isolates from food. The study was conducted on strains of the species S. epidermidis, S. heamolyticus, S. saprophyticus, and S. aureus. The values of the minimum inhibitory concentration against erythromycin, tetracycline, and oxacillin were determined before and after the incubation of the tested strains under stress conditions. The ability to form biofilm and slime production was also investigated. The expression levels of the genes responsible for antibiotic resistance (blaZ, tetK, tetM, ermB, and mecA) and virulence (eno) were conducted using Real-Time PCR. The MIC values of the antibiotics tested against the strains analyzed were found to be elevated in the presence of SICs of benzalkonium chloride and cadmium chloride. Furthermore, the intensity of biofilm production was also increased. SICs of benzalkonium chloride induced the expression of the tetM, tetK, mecA, and blaZ genes in 75%, 66.6%, 33.3%, and 40% of the isolates tested, respectively. Similar treatment with cadmium chloride induced the expression of the same genes in 75%, 100%, 66.6%, and 40% of the strains. In both cases, the expression of the ermB gene was reduced in 100% of the isolates. The eno gene was found to be overexpressed in 66.6% of the strains following benzalkonium chloride stress, and in 100% of the strains following cadmium chloride stress. These findings suggest that in Staphylococcus spp. strains, changes in the expression of the genes encoding antibiotic resistance and virulence factors may occur in response to the applied stress factors. The results indicate the possibility of selecting more resistant and virulent strains due to the use of too low concentrations of disinfectants, which emphasizes the need to use appropriate inhibitory doses of disinfectants in the food industry. Full article
(This article belongs to the Special Issue Antibacterial Activity against Drug-Resistant Strains, 2nd Edition)
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17 pages, 7075 KiB  
Article
Anti-Biofilm Activity of Oleacein and Oleocanthal from Extra-Virgin Olive Oil toward Pseudomonas aeruginosa
by Marisa Di Pietro, Simone Filardo, Roberto Mattioli, Giuseppina Bozzuto, Giammarco Raponi, Luciana Mosca and Rosa Sessa
Int. J. Mol. Sci. 2024, 25(9), 5051; https://doi.org/10.3390/ijms25095051 - 6 May 2024
Cited by 3 | Viewed by 2048
Abstract
New antimicrobial molecules effective against Pseudomonas aeruginosa, known as an antibiotic-resistant “high-priority pathogen”, are urgently required because of its ability to develop biofilms related to healthcare-acquired infections. In this study, for the first time, the anti-biofilm and anti-virulence activities of a polyphenolic [...] Read more.
New antimicrobial molecules effective against Pseudomonas aeruginosa, known as an antibiotic-resistant “high-priority pathogen”, are urgently required because of its ability to develop biofilms related to healthcare-acquired infections. In this study, for the first time, the anti-biofilm and anti-virulence activities of a polyphenolic extract of extra-virgin olive oil as well as purified oleocanthal and oleacein, toward P. aeruginosa clinical isolates were investigated. The main result of our study was the anti-virulence activity of the mixture of oleacein and oleocanthal toward multidrug-resistant and intermediately resistant strains of P. aeruginosa isolated from patients with ventilator-associated pneumonia or surgical site infection. Specifically, the mixture of oleacein (2.5 mM)/oleocanthal (2.5 mM) significantly inhibited biofilm formation, alginate and pyocyanin production, and motility in both P. aeruginosa strains (p < 0.05); scanning electron microscopy analysis further evidenced its ability to inhibit bacterial cell adhesion as well as the production of the extracellular matrix. In conclusion, our results suggest the potential application of the oleacein/oleocanthal mixture in the management of healthcare-associated P. aeruginosa infections, particularly in the era of increasing antimicrobial resistance. Full article
(This article belongs to the Special Issue Antibacterial Activity against Drug-Resistant Strains, 2nd Edition)
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