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Antibiotics
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Bacterial Pathogenesis and Antimicrobial Strategy
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Bacterial Pathogenesis and Antimicrobial Strategy

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Mechanism and Evolution of Antibiotic Resistance".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 13291

Special Issue Editors

Dr. Juan C. Vázquez-Ucha

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Guest Editor
Servicio de Microbiología, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario A Coruña (CHUAC), A Coruña, Spain
Interests: antimicrobial resistance; bacterial pathogenesis; antibiotics; beta-lactamase inhibitors; nosocomial pathogens; Gram-negative bacteria
Special Issues, Collections and Topics in MDPI journals
Dr. Marta Martínez-Guitián

E-Mail Website
Guest Editor
Servicio de Microbiología, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario A Coruña (CHUAC), A Coruña, Spain
Interests: new therapeutic targets; antimicrobial peptides; Acinetobacter baumannii; colistin resistance; animal models; antimicrobial resistance

Special Issue Information

Dear Colleagues,

Antibiotic resistance a major global health problem. The emergence of infections caused by multidrug-resistant (MDR) pathogens is becoming increasingly common, including the identification of strains resistant to all or almost all available drugs (pan-drug resistance, PDR). Microorganisms have a wide arsenal of antimicrobial resistance mechanisms, many of which are easily transmissible. Moreover, bacteria also produce a variety of virulence factors that enhance colonisation of the host and the development of infection, such as the presence of pilus or flagella, capsule formation, toxins production, or biofilm development, among others. Many of these virulence factors are also transmissible between pathogens. Therefore, the course of an infection and the success of treatment depend, in large part, on the resistance and virulence mechanisms that a pathogen carries.

This Special Issue aims to provide new insights into bacterial pathogenesis and antimicrobial resistance in both Gram-positive and Gram-negative bacteria. In particular, we will focus on (i) the identification and description of new resistance mechanisms and/or virulence factors, (ii) the activity of new antimicrobials or antivirulence compounds, (iii) the relationship between virulence and antimicrobial resistance, and (iv) the identification and description of new therapeutic targets. Research papers, communications, short notes, and reviews related to these topics are welcome for this Special Issue.

Dr. Juan C. Vázquez-Ucha
Dr. Marta Martínez-Guitián
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • antibiotics
  • antimicrobials
  • antimicrobial resistance
  • virulence factors
  • antivirulence compounds
  • new therapeutic targets
  • antibacterial agents
  • infection
  • treatment

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Published Papers (6 papers)

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Editorial

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3 pages, 211 KiB  
Editorial
Bacterial Pathogenesis and Antimicrobial Strategy
by Juan C. Vázquez-Ucha and Marta Martínez-Guitián
Antibiotics 2023, 12(12), 1750; https://doi.org/10.3390/antibiotics12121750 - 18 Dec 2023
Viewed by 1286
Abstract
Antimicrobial resistance and multidrug resistance are major global health concerns [...] Full article
(This article belongs to the Special Issue Bacterial Pathogenesis and Antimicrobial Strategy)

Research

Jump to: Editorial

12 pages, 1040 KiB  
Article
Interplay between OXA-10 β-Lactamase Production and Low Outer-Membrane Permeability in Carbapenem Resistance in Enterobacterales
by Isaac Alonso-García, Juan Carlos Vázquez-Ucha, Marta Martínez-Guitián, Cristina Lasarte-Monterrubio, Salud Rodríguez-Pallares, Pablo Camacho-Zamora, Soraya Rumbo-Feal, Pablo Aja-Macaya, Lucía González-Pinto, Michelle Outeda-García, Romina Maceiras, Paula Guijarro-Sánchez, María José Muíño-Andrade, Ana Fernández-González, Marina Oviaño, Concepción González-Bello, Jorge Arca-Suárez, Alejandro Beceiro and Germán Bou
Antibiotics 2023, 12(6), 999; https://doi.org/10.3390/antibiotics12060999 - 1 Jun 2023
Cited by 3 | Viewed by 1767
Abstract
The OXA-10 class D β-lactamase has been reported to contribute to carbapenem resistance in non-fermenting Gram-negative bacilli; however, its contribution to carbapenem resistance in Enterobacterales is unknown. In this work, minimum inhibitory concentrations (MICs), whole genome sequencing (WGS), cloning experiments, kinetic assays, molecular [...] Read more.
The OXA-10 class D β-lactamase has been reported to contribute to carbapenem resistance in non-fermenting Gram-negative bacilli; however, its contribution to carbapenem resistance in Enterobacterales is unknown. In this work, minimum inhibitory concentrations (MICs), whole genome sequencing (WGS), cloning experiments, kinetic assays, molecular modelling studies, and biochemical assays for carbapenemase detection were performed to determine the impact of OXA-10 production on carbapenem resistance in two XDR clinical isolates of Escherichia coli with the carbapenem resistance phenotype (ertapenem resistance). WGS identified the two clinical isolates as belonging to ST57 in close genomic proximity to each other. Additionally, the presence of the blaOXA-10 gene was identified in both isolates, as well as relevant mutations in the genes coding for the OmpC and OmpF porins. Cloning of blaOXA-10 in an E. coli HB4 (OmpC and OmpF-deficient) demonstrated the important contribution of OXA-10 to increased carbapenem MICs when associated with porin deficiency. Kinetic analysis showed that OXA-10 has low carbapenem-hydrolysing activity, but molecular models revealed interactions of this β-lactamase with the carbapenems. OXA-10 was not detected with biochemical tests used in clinical laboratories. In conclusion, the β-lactamase OXA-10 limits the activity of carbapenems in Enterobacterales when combined with low permeability and should be monitored in the future. Full article
(This article belongs to the Special Issue Bacterial Pathogenesis and Antimicrobial Strategy)
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10 pages, 842 KiB  
Article
In Vitro Activity of Imipenem-Relebactam, Meropenem-Vaborbactam, Ceftazidime-Avibactam and Comparators on Carbapenem-Resistant Non-Carbapenemase-Producing Enterobacterales
by Rémy A. Bonnin, Sandrine Bernabeu, Cécile Emeraud, Thierry Naas, Delphine Girlich, Agnès B. Jousset and Laurent Dortet
Antibiotics 2023, 12(1), 102; https://doi.org/10.3390/antibiotics12010102 - 6 Jan 2023
Cited by 10 | Viewed by 2512
Abstract
Background: Avibactam, relebactam and vaborbactam are β-lactamase inhibitors that proved their efficiency against KPC-producing Enterobacterales. Regarding their inhibitor activity towards Ambler’s class A extended spectrum β-lactamases (ESBL) and Ambler’s class C cephalosporinase (AmpC), they should be active on most of the carbapenem-resistant non-carbapenemase-producing [...] Read more.
Background: Avibactam, relebactam and vaborbactam are β-lactamase inhibitors that proved their efficiency against KPC-producing Enterobacterales. Regarding their inhibitor activity towards Ambler’s class A extended spectrum β-lactamases (ESBL) and Ambler’s class C cephalosporinase (AmpC), they should be active on most of the carbapenem-resistant non-carbapenemase-producing Enterobacterales (CR non-CPE). Objectives: Determine the in vitro activity of ceftazidime-avibactam, imipenem-relebactam and meropenem-vaborbactam and comparators against CR non-CPE. Methods: MICs to ceftazidime/avibactam, imipenem/relebactam, meropenem/vaborbactam, but also temocillin, ceftolozane/tazobactam, ertapenem, colistin, eravacycline and tigecycline were determined by broth microdilution (ThermoFisher) on a collection of 284 CR non-CPE (inhibition zone diameter < 22 mm to meropenem). Whole genome sequencing was performed on 90 isolates to assess the genetic diversity as well as resistome. Results: According to EUCAST breakpoints, susceptibility rates of ceftazidime, imipenem, meropenem and ertapenem used at standard dose were 0.7%, 45.1%, 14.8% and 2.5%, respectively. Increased exposure of ceftazidime, imipenem and meropenem led to reach 3.5%, 68.3% and 67.7% susceptibility, respectively. Using the EUCAST clinical breakpoints, susceptibility rates of ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam were 88.4%, 81.0% and 80.6%, respectively. Susceptibility rates of temocillin, ceftolozane/tazobactam, tigecycline, eravacycline, and colistin were 0%, 4.6%, 27.8%, 54.9% and 90.1%. MICs distributions with and without the presence of the inhibitor demonstrated a better ability of avibactam and relebactam compared to vaborbactam to restore susceptibility to the associated β-lactam. Conclusions: This study demonstrated the in vitro efficacy of ceftazidime/avibactam, imipenem/relebactam and to a lesser extent meropenem/vaborbactam against CR non-CPE. Moreover, to test all β-lactams/β-lactamases inhibitors combinations without a priori for CRE, non-CPE is crucial since resistance to one of the β-lactam/β-lactamase inhibitor combinations does not predict resistance to another molecule, depending on the resistance mechanisms involved. Full article
(This article belongs to the Special Issue Bacterial Pathogenesis and Antimicrobial Strategy)
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14 pages, 17368 KiB  
Article
Controlling of Bacterial Virulence: Evaluation of Anti-Virulence Activities of Prazosin against Salmonella enterica
by Mahmoud A. Elfaky, Abrar K. Thabit, Khalid Eljaaly, Ayat Zawawi, Ahmed S. Abdelkhalek, Ahmad J. Almalki, Tarek S. Ibrahim and Wael A. H. Hegazy
Antibiotics 2022, 11(11), 1585; https://doi.org/10.3390/antibiotics11111585 - 9 Nov 2022
Cited by 16 | Viewed by 2000
Abstract
Salmonella enterica is a Gram-negative orofecal transmitted pathogen that causes a wide diversity of local and systemic illnesses. Salmonella enterica utilizes several interplayed systems to regulate its invasion and pathogenesis: namely, quorum sensing (QS) and type three secretion system (T3SS). In addition, S. [...] Read more.
Salmonella enterica is a Gram-negative orofecal transmitted pathogen that causes a wide diversity of local and systemic illnesses. Salmonella enterica utilizes several interplayed systems to regulate its invasion and pathogenesis: namely, quorum sensing (QS) and type three secretion system (T3SS). In addition, S. enterica could sense the adrenergic hormones in the surroundings that enhance its virulence. The current study aimed to evaluate the ability of α-adrenoreceptor antagonist prazosin to mitigate the virulence of S. enterica serovar Typhimurium. The prazosin effect on biofilm formation and the expression of sdiA, qseC, qseE, and T3SS-type II encoding genes was evaluated. Furthermore, the prazosin intracellular replication inside macrophage and anti-virulence activity was evaluated in vivo against S. typhimurium. The current finding showed a marked prazosin ability to compete on SdiA and QseC and downregulate their encoding genes. Prazosin significantly downregulated the virulence factors encoding genes and diminished the biofilm formation, intracellular replication inside macrophages, and in vivo protected mice. To sum up, prazosin showed significant inhibitory activities against QS, T3SS, and bacterial espionage, which documents its considered anti-virulence activities. Full article
(This article belongs to the Special Issue Bacterial Pathogenesis and Antimicrobial Strategy)
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10 pages, 281 KiB  
Article
Whole-Genome Sequencing of ST2 A. baumannii Causing Bloodstream Infections in COVID-19 Patients
by Sabrina Cherubini, Mariagrazia Perilli, Bernardetta Segatore, Paolo Fazii, Giustino Parruti, Antonella Frattari, Gianfranco Amicosante and Alessandra Piccirilli
Antibiotics 2022, 11(7), 955; https://doi.org/10.3390/antibiotics11070955 - 15 Jul 2022
Cited by 19 | Viewed by 2448
Abstract
A total of 43 A. baumannii strains, isolated from 43 patients affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and by bacterial sepsis, were analyzed by antimicrobial susceptibility testing. All strains were resistant to almost three different classes of antibiotics, including carbapenems [...] Read more.
A total of 43 A. baumannii strains, isolated from 43 patients affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and by bacterial sepsis, were analyzed by antimicrobial susceptibility testing. All strains were resistant to almost three different classes of antibiotics, including carbapenems and colistin. The whole-genome sequencing (WGS) of eight selected A. baumannii isolates showed the presence of different insertion sequences (ISs), such as ISAba13, ISAba26, IS26, ISVsa3, ISEc29, IS6100 and IS17, giving to A. baumannii a high ability to capture and mobilize antibiotic resistance genes. Resistance to carbapenems is mainly mediated by the presence of OXA-23, OXA-66 and OXA-82 oxacillinases belonging to OXA-51-like enzymes. The presence of AmpC cephalosporinase, ADC-25, was identified in all A. baumannii. The pathogenicity of A. baumannii was exacerbated by the presence of several virulence factors. The multi-locus sequence typing (MLST) analysis showed that all strains belong to sequence type 2 (ST) international clone. Full article
(This article belongs to the Special Issue Bacterial Pathogenesis and Antimicrobial Strategy)
12 pages, 1228 KiB  
Article
Characterization of Diarreaghenic Escherichia coli Strains Isolated from Healthy Donors, including a Triple Hybrid Strain
by Evelyn Méndez-Moreno, Liliana Caporal-Hernandez, Pablo A. Mendez-Pfeiffer, Yessica Enciso-Martinez, Rafael De la Rosa López, Dora Valencia, Margarita M. P. Arenas-Hernández, Manuel G. Ballesteros-Monrreal and Edwin Barrios-Villa
Antibiotics 2022, 11(7), 833; https://doi.org/10.3390/antibiotics11070833 - 21 Jun 2022
Cited by 7 | Viewed by 2340
Abstract
Escherichia coli is a well-recognized inhabitant of the animal and human gut. Its presence represents an essential component of the microbiome. There are six pathogenic variants of E. coli associated with diarrheal processes, known as pathotypes. These harbor genetic determinants that allow them [...] Read more.
Escherichia coli is a well-recognized inhabitant of the animal and human gut. Its presence represents an essential component of the microbiome. There are six pathogenic variants of E. coli associated with diarrheal processes, known as pathotypes. These harbor genetic determinants that allow them to be classified as such. In this work, we report the presence of diarrheagenic pathotypes of E. coli strains isolated from healthy donors. Ninety E. coli strains were analyzed, of which forty-six (51%) harbored virulence markers specifics for diarrheagenic pathotypes, including four hybrids (one of them with genetic determinants of three DEC pathotypes). We also identified phylogenetic groups with a higher prevalence of B2 (45.6%) and A (17.8%). In addition, resistance to sulfonamides (100%), and aminoglycosides (100%) was found in 100% of the strains, with a lower prevalence of resistance to cefotaxime (13.3%), ceftriaxone (12.2%), fosfomycin (10%), and meropenem (0%). All analyzed strains were classified as multidrug resistant. Virulence genes were also investigated, which led us to propose three new virotypes. Among the virulence traits observed, the ability to form biofilms stands out, which was superior to that of the E. coli and Staphylococcus aureus strains used as positive controls. Full article
(This article belongs to the Special Issue Bacterial Pathogenesis and Antimicrobial Strategy)
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