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Pathogens
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Virulence and Resistance Mechanisms in Multidrug-Resistant Gram-Negative Bacteria
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Virulence and Resistance Mechanisms in Multidrug-Resistant Gram-Negative Bacteria

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Bacterial Pathogens".

Deadline for manuscript submissions: closed (31 March 2025) | Viewed by 8650

Special Issue Editors

Dr. Steven E. Fiester

E-Mail Website
Guest Editor
1. Department of Chemistry, Furman University, Greenville, SC 29613, USA
2. Department of Pathology, Prisma Health, School of Health Science Research, Clemson University, Clemson, SC 29634, USA
3. Dorn Research Institute, Wm. Jennings Bryan Dorn VA Medical Center, Columbia, SC 29209, USA
Interests: Acinetobacter; Klebsiella; drug discovery; antimicrobial stewardship; virulence factors; infectious diseases; bacteriology
Special Issues, Collections and Topics in MDPI journals
Dr. William Penwell

E-Mail Website
Guest Editor
Department of Biology and Marine Science, Jacksonville University, Jacksonville, Fl, USA
Interests: Acinetobacter; Stenotrophomonas; drug discovery; virulence factors; infectious diseases; bacterial iron-acquisition
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Carmelo Biondo

E-Mail Website
Guest Editor
Department of Human Pathology, University of Messina, 98100 Messina, Italy
Interests: host-pathogen interactions; bacterial infection; vaccines; medical mycology; innate immunity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We invite you to submit your research characterizing virulence and/or resistance mechanisms in Gram-negative bacteria for publication consideration in this Special Issue of Pathogens. Gram-negative infections cause a substantial burden to patients globally, resulting in significant morbidity and mortality. This is reflected by data from both the U.S. Centers for Disease Control and Prevention and the World Health Organization in their reports on antibiotic-resistant threats and priority pathogens, respectively, wherein many of the pathogens noted are Gram-negative. While much is known about many of these pathogens, novel therapeutics to combat these bacteria in the healthcare setting are lacking, mainly due to a lack of data pertaining to their underlying virulence and resistance mechanisms. This sparsity of data makes the discovery of therapeutic targets difficult, stifling drug development. This Special Issue therefore encourages submissions of original research that closes this gap by elucidating the virulence and resistance mechanisms of these critically important bacteria, ultimately aiding in the discovery of novel therapeutic targets.

Dr. Steven E. Fiester
Dr. William Penwell
Dr. Carmelo Biondo
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. Pathogens 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 2200 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

  • antibiotic resistance mechanisms
  • MDR gram-negative bacteria
  • gram-negative nosocomial infections
  • carbapenem-resistant Enterobacteriaceae infections
  • bacterial infection

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Published Papers (5 papers)

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Research

19 pages, 1944 KiB  
Article
Antibiotic Susceptibility Patterns and Virulence Profiles of Classical and Hypervirulent Klebsiella pneumoniae Strains Isolated from Clinical Samples in Khyber Pakhtunkhwa, Pakistan
by Azra, Taj Ali Khan, Ihtisham Ul Haq, Woranich Hinthong, Susana Campino, Aisha Gohar, Noman Khan, Muhammad Kashif, Ihsan Ullah and Taane G. Clark
Pathogens 2025, 14(1), 79; https://doi.org/10.3390/pathogens14010079 - 15 Jan 2025
Viewed by 1493
Abstract
The emergence of hypervirulent and carbapenem-resistant hypermucoviscous Klebsiella pneumoniae strains presents a significant public health challenge due to their increased virulence and resistance to multiple antibiotics. This study evaluates the antibiotic susceptibility patterns and virulence profiles of classical and hypervirulent K. pneumoniae strains [...] Read more.
The emergence of hypervirulent and carbapenem-resistant hypermucoviscous Klebsiella pneumoniae strains presents a significant public health challenge due to their increased virulence and resistance to multiple antibiotics. This study evaluates the antibiotic susceptibility patterns and virulence profiles of classical and hypervirulent K. pneumoniae strains isolated from various clinical samples. A total of 500 clinical samples were collected from patients at the Mardan Medical Complex and Ayub Medical Complex in KPK between July 2022 and June 2024. Among these, 64 K. pneumoniae strains were isolated and subsequently subjected to antimicrobial susceptibility testing (AST) and phenotypic virulence detection. Among the 64 isolates, 21 (32.8%) exhibited hypermucoviscosity, a characteristic associated with increased pathogenicity. Hemagglutination was observed in 35 (54.1%) of the isolates, indicating the presence of surface adhesins that facilitate bacterial adherence to host tissues. A high prevalence of biofilm formation was noted, with 54 (84%) isolates capable of forming biofilms, which are known to protect bacteria from antibiotics and the host immune response. Most isolates (59/64, 92.1%) were resistant against ampicillin, highlighting its limited efficacy against these strains. Conversely, the lowest resistance was observed for tigecycline, with only 15% (10/64) of the isolates showing resistance, indicating its potential utility as a treatment option. The study also found that 38 (59.3%) of the isolates were extended-spectrum beta-lactamase (ESBL) producers, 42 (65.6%) were multidrug-resistant (MDR), 32 (50%) were extensively drug-resistant (XDR), and 13 (20.3%) were resistant to carbapenems. The genetic study revealed biofilm producer and enhancer genes (mrkD, pgaABCD, fimH, treC, wzc, pilQ, and luxS) mainly in the hypervirulent strains. These hypervirulent strains also show a high number of resistance genes. The findings of this study underscore the critical need for the active surveillance of antimicrobial resistance and virulence determinants in K. pneumoniae. The coexistence of high levels of antibiotic resistance and virulence factors in these isolates poses a severe threat to public health, as it can lead to difficult-to-treat infections and increased morbidity and mortality. Full article
(This article belongs to the Special Issue Virulence and Resistance Mechanisms in Multidrug-Resistant Gram-Negative Bacteria)
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14 pages, 3787 KiB  
Article
A Four-Year Study of Antibiotic Resistance, Prevalence and Biofilm-Forming Ability of Uropathogens Isolated from Community- and Hospital-Acquired Urinary Tract Infections in Southern Italy
by Marilena Trinchera, Angelina Midiri, Giuseppe Mancuso, Maria Antonietta Lagrotteria, Carmelo Antonio De Ani and Carmelo Biondo
Pathogens 2025, 14(1), 59; https://doi.org/10.3390/pathogens14010059 - 11 Jan 2025
Cited by 1 | Viewed by 1503
Abstract
The aim of this study was to investigate the differences between nosocomial and community microorganisms isolated from patients with UTI by determining their bacterial profile, antibiotic resistance and ability to produce biofilms. A retrospective study, based on bacterial isolates from consecutive urine samples [...] Read more.
The aim of this study was to investigate the differences between nosocomial and community microorganisms isolated from patients with UTI by determining their bacterial profile, antibiotic resistance and ability to produce biofilms. A retrospective study, based on bacterial isolates from consecutive urine samples collected between January 2019 and December 2023, was conducted at a university hospital. The main pathogens isolated from both community and hospital samples were the same, but their frequency of isolation differed. Compared with community-associated cases, hospital-associated infections have more isolates of Acinetobacter baumanii complex. In contrast, Proteus mirabilis isolates were more prevalent in community than in hospital infections. In both hospital and community isolates, gram-positive bacteria showed a lower overall antimicrobial resistance (22%) compared to gram-negative bacteria (30%). The data demonstrated that individual strains exhibited disparate degrees of capacity for biofilm formation. Additionally, the data indicate an inverse correlation between biofilm production and antibiotic resistance. Isolates from community patients exhibited lower capacities for biofilm production in comparison to the capacities demonstrated by microorganisms isolated from nosocomial patients (29% and 35%, respectively). Area-specific surveillance studies can provide valuable information on UTI pathogens and antimicrobial resistance patterns, which can be useful in guiding empirical treatment. Full article
(This article belongs to the Special Issue Virulence and Resistance Mechanisms in Multidrug-Resistant Gram-Negative Bacteria)
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18 pages, 7582 KiB  
Article
Phylogenetics and Mobilization of Genomic Traits of Cephalosporin-Resistant Escherichia coli Originated from Retail Meat
by Ewelina Iwan, Magdalena Zając, Arkadiusz Bomba, Małgorzata Olejnik, Magdalena Skarżyńska, Bernard Wasiński, Kinga Wieczorek, Katarzyna Tłuścik and Dariusz Wasyl
Pathogens 2024, 13(8), 700; https://doi.org/10.3390/pathogens13080700 - 19 Aug 2024
Viewed by 1253
Abstract
Contaminations with cephalosporin-resistant Escherichia coli across the food chain may pose a significant threat to public health because those antimicrobials are critically important in human medicine. The impact of the presented data is especially significant concerning Poland’s role as one of the leading [...] Read more.
Contaminations with cephalosporin-resistant Escherichia coli across the food chain may pose a significant threat to public health because those antimicrobials are critically important in human medicine. The impact of the presented data is especially significant concerning Poland’s role as one of the leading food producers in the EU. This work aimed to characterize the genomic contents of cephalosporin-resistant Escherichia coli (n = 36) isolated from retail meat to expand the official AMR monitoring reported by EFSA. The ESBL mechanism was predominant (via blaCTX-M-1 and blaSHV-12), with the AmpC-type represented by the blaCMY-2 variant. The strains harbored multiple resistance genes, mainly conferring resistance to aminoglycosides, sulfonamides, trimethoprim, tetracyclines. In some isolates, virulence factors—including intimin (eae) and its receptor (tir) were detected, indicating significant pathogenic potential. Resistance genes showed a link with IncI1 and IncB/O/K/Z plasmids. Cephalosporinases were particularly linked to ISEc9/ISEc1 (blaCTX-M-1 and blaCMY-2). The association of virulence with mobile elements was less common—mostly with IncF plasmids. The analysis of E. coli isolated from retail meat indicates accumulation of ARGs and their association with various mobile genetic elements, thus increasing the potential for the transmission of resistance across the food chain. Full article
(This article belongs to the Special Issue Virulence and Resistance Mechanisms in Multidrug-Resistant Gram-Negative Bacteria)
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16 pages, 1768 KiB  
Article
A Health Threat from Farm to Fork: Shiga Toxin-Producing Escherichia coli Co-Harboring blaNDM-1 and mcr-1 in Various Sources of the Food Supply Chain
by Ayesha Sarwar, Bilal Aslam, Muhammad Hidayat Rasool, Mounir M. Salem Bekhit and James Sasanya
Pathogens 2024, 13(8), 659; https://doi.org/10.3390/pathogens13080659 - 6 Aug 2024
Cited by 1 | Viewed by 1388
Abstract
The dissemination of resistant pathogens through food supply chains poses a significant public health risk, spanning from farm to fork. This study analyzed the distribution of Shiga toxin-producing Escherichia coli (STEC) across various sources within the animal-based food supply chain. A total of [...] Read more.
The dissemination of resistant pathogens through food supply chains poses a significant public health risk, spanning from farm to fork. This study analyzed the distribution of Shiga toxin-producing Escherichia coli (STEC) across various sources within the animal-based food supply chain. A total of 500 samples were collected from livestock, poultry, the environment, fisheries, and dairy. Standard microbiological procedures were employed to isolate and identify E. coli isolates, which were further confirmed using MALDI-TOF and virulence-associated genes (VAGs) such as stx1, stx2, ompT, hylF, iutA, fimH, and iss. The phenotypic resistance patterns of the isolates were determined using the disc diffusion method, followed by molecular identification of antibiotic resistance genes (ARGs) through PCR. STEC were subjected to PCR-based O typing using specific primers for different O types. Overall, 154 (30.5%) samples were confirmed as E. coli, of which 77 (50%) were multidrug-resistant (MDR) E. coli. Among these, 52 (67.53%) isolates exhibited an array of VAGs, and 21 (40.38%) were confirmed as STEC based on the presence of stx1 and stx2. Additionally, 12 out of 52 (23.07%) isolates were identified as non-O157 STEC co-harbouring mcr-1 and blaNDM-1. O26 STEC was found to be the most prevalent among the non-O157 types. The results suggest that the detection of STEC in food supply chains may lead to serious health consequences, particularly in developing countries with limited healthcare resources. Full article
(This article belongs to the Special Issue Virulence and Resistance Mechanisms in Multidrug-Resistant Gram-Negative Bacteria)
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16 pages, 940 KiB  
Article
Multidrug-Resistant Bacteria in Surgical Intensive Care Units: Antibiotic Susceptibility and β-Lactamase Characterization
by Daniela Bandić Pavlović, Mladen Pospišil, Marina Nađ, Vilena Vrbanović Mijatović, Josefa Luxner, Gernot Zarfel, Andrea Grisold, Dinko Tonković, Mirela Dobrić and Branka Bedenić
Pathogens 2024, 13(5), 411; https://doi.org/10.3390/pathogens13050411 - 15 May 2024
Cited by 1 | Viewed by 2110
Abstract
Multidrug-resistant (MDR) bacteria of the utmost importance are extended-spectrum β-lactamase (ESBL) and carbapenemase-producing Enterobacterales (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus spp. (VRE). In this study, an evaluation of MDR bacteria in surgical intensive [...] Read more.
Multidrug-resistant (MDR) bacteria of the utmost importance are extended-spectrum β-lactamase (ESBL) and carbapenemase-producing Enterobacterales (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus spp. (VRE). In this study, an evaluation of MDR bacteria in surgical intensive care units in a tertiary referral hospital was conducted. The study aimed to characterize β-lactamases and other resistance traits of Gram-negative bacteria isolated in surgical intensive care units (ICUs). Disk diffusion and the broth dilution method were used for antibiotic susceptibility testing, whereas ESBL screening was performed through a double disk synergy test and an inhibitor-based test with clavulanic acid. A total of 119 MDR bacterial isolates were analysed. ESBL production was observed in half of the Proteus mirabilis, 90% of the Klebsiella pneumoniae and all of the Enterobacter cloacae and Escherichia coli isolates. OXA-48 carbapenemase, carried by the L plasmid, was detected in 34 K. pneumoniae and one E. coli and Enterobacter cloacae complex isolates, whereas NDM occurred sporadically and was identified in three K. pneumoniae isolates. OXA-48 positive isolates coharboured ESBLs belonging to the CTX-M family in all but one isolate. OXA-23 carbapenemase was confirmed in all A. baumannii isolates. The findings of this study provide valuable insight of resistance determinants of Enterobacterales and A. baumannii which will enhance surveillance and intervention strategies that are necessary to curb the ever-growing carbapenem resistance rates. Full article
(This article belongs to the Special Issue Virulence and Resistance Mechanisms in Multidrug-Resistant Gram-Negative Bacteria)
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