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Antibiotics
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Antibiotics Resistance in Gram-Negative Bacteria, 2nd Edition
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Antibiotics Resistance in Gram-Negative Bacteria, 2nd Edition

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: 15 May 2025 | Viewed by 10615

Special Issue Editor

Prof. Dr. Simone Simionatto

E-Mail Website
Guest Editor
Laboratório de Pesquisa em Ciências da Saúde, Universidade Federal da Grande Dourados-UFGD, Dourados, Mato Grosso do Sul, Brazil
Interests: antibiotic resistance; molecular epidemiology of Gram-negative bacteria; antimicrobial effects of natural products on bacteria; antisense therapy; drug repositioning
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Antimicrobial resistance has been recognized as one of the most serious global threats to human health. The ability of Gram-negative bacteria to acquire resistance to antimicrobials via horizontal gene transfer and mutation is a real threat and a burden on human health and the economy. Even though they are most commonly detected in hospital settings, multi-drug-resistant Gram-negative bacteria have also been described in other ecological niches. The epidemiology of Gram-negative bacteria is complex and the importance of an integrated surveillance system based on the One-Health approach has been widely recognized. The use of antimicrobials in medicine, agriculture and livestock has favored the selection of these pathogens. In addition, increased hospitalization and the indiscriminate use of antimicrobials during the COVID-19 pandemic may have contributed to increased rates of multi-drug-resistant Gram-negative bacteria. Thus, the effects of antimicrobial resistance on public health and the economy in the short and medium term are concerning. Efforts must be taken to implement new policies and control programs on how to use and dispense antibiotics. Furthermore, understanding the resistance mechanisms and epidemiology of bacteria is critical for the development of novel antibacterials, which are needed to meet future demands. This Special Issue seeks manuscript submissions that further our understanding of the epidemiology and antimicrobial resistance of Gram-negative bacteria. Submissions on the search for new drugs developed through structural modification agents, the production of synthetic derivatives or repositioning are especially encouraged.

Prof. Dr. Simone Simionatto
Guest Editor

Manuscript Submission Information

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Keywords

  • antimicrobial resistance
  • epidemiology
  • genomics surveillance
  • One-Health
  • enterobacteriaceae
  • repurposing
  • bacteriophages
  • antimicrobial peptides
  • natural compounds
  • virulence profiles

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Published Papers (5 papers)

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Research

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15 pages, 2762 KiB  
Article
Investigating the Antimicrobial Potential of 560 Compounds from the Pandemic Response Box and COVID Box against Resistant Gram-Negative Bacteria
by Rita de Cássia Cerqueira Melo, Aline Andrade Martins, Andressa Leite Ferraz Melo, Jean Carlos Pael Vicente, Mariana Carvalho Sturaro, Julia Pimentel Arantes, Luana Rossato, Gleyce Hellen de Almeida de Souza and Simone Simionatto
Antibiotics 2024, 13(8), 723; https://doi.org/10.3390/antibiotics13080723 - 1 Aug 2024
Viewed by 1077
Abstract
Antimicrobial resistance (AMR) has emerged as a significant threat to public health, particularly in infections caused by critically important Gram-negative bacteria. The development of novel antibiotics has its limitations, and therefore it is crucial to explore alternative strategies to effectively combat infections with [...] Read more.
Antimicrobial resistance (AMR) has emerged as a significant threat to public health, particularly in infections caused by critically important Gram-negative bacteria. The development of novel antibiotics has its limitations, and therefore it is crucial to explore alternative strategies to effectively combat infections with resistant pathogens. In this context, the present study investigated the antibacterial potency of 560 compounds against the multidrug-resistant (MDR) strains of Klebsiella pneumoniae and Serratia marcescens. The evaluated compounds were selected from the Pandemic Response Box (PRB) and COVID Box (CB) and subjected to assays to determine the inhibitory concentration (IC), minimum bactericidal concentration (MBC), and biofilm formation. Further, the effects of these compounds on membrane integrity were assessed through protein quantification. Several of the evaluated compounds, including fusidic acid, MMV1580853, and MMV1634399, exhibited a significant reduction in biofilm formation and growth in K. pneumoniae. Trimethoprim exhibited potential against S. marcescens. The IC values of the compounds indicated significant microbial growth inhibition at various concentrations. These findings underscore the potency of the existing antibiotics and novel compounds in combating the MDR strains of bacteria. The importance of reconsidering the known antibiotics and utilizing drug repositioning strategies to address the increasing risk of AMR is highlighted. Full article
(This article belongs to the Special Issue Antibiotics Resistance in Gram-Negative Bacteria, 2nd Edition)
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19 pages, 1128 KiB  
Article
Analyses of Extended-Spectrum-β-Lactamase, Metallo-β-Lactamase, and AmpC-β-Lactamase Producing Enterobacteriaceae from the Dairy Value Chain in India
by Tushar Kumar Dey, Johanna Frida Lindahl, Åke Lundkvist, Delia Grace, Ram Pratim Deka, Rajeswari Shome, Samiran Bandyopadhyay, Naresh Kumar Goyal, Garima Sharma and Bibek Ranjan Shome
Antibiotics 2023, 12(9), 1449; https://doi.org/10.3390/antibiotics12091449 - 14 Sep 2023
Cited by 2 | Viewed by 2346
Abstract
The consumption of milk contaminated with antibiotic-resistant bacteria poses a significant health threat to humans. This study aimed to investigate the prevalence of Enterobacteriaceae producing β-lactamases (ESBL, MBL, and AmpC) in cow and buffalo milk samples from two Indian states, Haryana and Assam. [...] Read more.
The consumption of milk contaminated with antibiotic-resistant bacteria poses a significant health threat to humans. This study aimed to investigate the prevalence of Enterobacteriaceae producing β-lactamases (ESBL, MBL, and AmpC) in cow and buffalo milk samples from two Indian states, Haryana and Assam. A total of 401 milk samples were collected from dairy farmers and vendors in the specified districts. Microbiological assays, antibiotic susceptibility testing, and PCR-based genotyping were employed to analyze 421 Gram-negative bacterial isolates. The overall prevalence of β-lactamase genes was 10% (confidence interval (CI) (7–13)), with higher rates in Haryana (13%, CI (9–19)) compared to Assam (7%, CI (4–11)). The identified β-lactamase genes in isolates were blaCMY, blaMOX, blaFOX, blaEBC, and blaDHA, associated with AmpC production. Additionally, blaCTX-M1, blaSHV, and blaTEM were detected as ESBL producers, while blaVIM, blaIMP, blaSPM, blaSIM, and blaGIM were identified as MBL producers. Notably, Shigella spp. were the dominant β-lactamase producers among identified Enterobacteriaceae. This study highlights the presence of various prevalent β-lactamase genes in milk isolates, indicating the potential risk of antimicrobial-resistant bacteria in dairy products. The presence of β-lactam resistance raises concern as this could restrict antibiotic options for treatment. The discordance between genotypic and phenotypic methods emphasizes the necessity for comprehensive approaches that integrate both techniques to accurately assess antibiotic resistance. Urgent collaborative action incorporating rational and regulated use of antibiotics across the dairy value chain is required to address the global challenge of β-lactam resistance. Full article
(This article belongs to the Special Issue Antibiotics Resistance in Gram-Negative Bacteria, 2nd Edition)
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18 pages, 12522 KiB  
Article
Comparative Transcriptomic Profiling of Pellicle and Planktonic Cells from Carbapenem-Resistant Acinetobacter baumannii
by Heng Kang Ng, Suat Moi Puah, Cindy Shuan Ju Teh, Nuryana Idris and Kek Heng Chua
Antibiotics 2023, 12(7), 1185; https://doi.org/10.3390/antibiotics12071185 - 13 Jul 2023
Viewed by 1750
Abstract
Acinetobacter baumannii forms air–liquid interface pellicles that boost its ability to withstand desiccation and increase survival under antibiotic pressure. This study aims to delve into the transcriptomic profiles of pellicle cells from clinical strains of carbapenem-resistant A. baumannii (CRAB). The total RNA was [...] Read more.
Acinetobacter baumannii forms air–liquid interface pellicles that boost its ability to withstand desiccation and increase survival under antibiotic pressure. This study aims to delve into the transcriptomic profiles of pellicle cells from clinical strains of carbapenem-resistant A. baumannii (CRAB). The total RNA was extracted from pellicle cells from three pellicle-forming CRAB strains and planktonic cells from three non-pellicle-forming CRAB strains, subject to RNA sequencing using Illumina HiSeq 2500 system. A transcriptomic analysis between pellicle and planktonic cells, along with differential expression genes (DEGs) analysis and enrichment analysis of annotated COGs, GOs, and KEGGs, was performed. Our analysis identified 366 DEGs in pellicle cells: 162 upregulated genes and 204 downregulated genes. The upregulated ABUW_1624 (yiaY) gene and downregulated ABUW_1550 gene indicated potential involvement in fatty acid degradation during pellicle formation. Another upregulated ABUW_2820 (metQ) gene, encoding the D-methionine transporter system, hinted at its contribution to pellicle formation. The upregulation of two-component systems, CusSR and KdpDE, which implies the regulation of copper and potassium ions in a CRAB pellicle formation was also observed. These findings provide valuable insights into the regulation of gene expression during the formation of pellicles in CRAB, and these are potential targets that may aid in the eradication of CRAB infections. Full article
(This article belongs to the Special Issue Antibiotics Resistance in Gram-Negative Bacteria, 2nd Edition)
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16 pages, 1357 KiB  
Article
Anaerobic Gram-Negative Bacteria: Role as a Reservoir of Antibiotic Resistance
by Anshul Sood, Pallab Ray and Archana Angrup
Antibiotics 2023, 12(5), 942; https://doi.org/10.3390/antibiotics12050942 - 22 May 2023
Cited by 3 | Viewed by 3361
Abstract
Background: Anaerobic Gram-negative bacteria (AGNB) play a significant role as both pathogens and essential members of the human microbiota. Despite their clinical importance, there remains limited understanding regarding their antimicrobial resistance (AMR) patterns. This knowledge gap poses challenges in effectively managing AGNB-associated infections, [...] Read more.
Background: Anaerobic Gram-negative bacteria (AGNB) play a significant role as both pathogens and essential members of the human microbiota. Despite their clinical importance, there remains limited understanding regarding their antimicrobial resistance (AMR) patterns. This knowledge gap poses challenges in effectively managing AGNB-associated infections, as empirical treatment approaches may not adequately address the evolving resistance landscape. To bridge this research gap, we conducted a comprehensive study aimed at exploring the role of human AGNB as a reservoir of AMR. This can provide valuable insights for the prevention and management of anaerobic infections. Methods: We studied the prevalence of AMR and AMR determinants conferring resistance to metronidazole (nimE), imipenem (cfiA), piperacillin–tazobactam (cepA), cefoxitin (cfxA), clindamycin (ermF), chloramphenicol (cat) and mobile genetic elements (MGEs) such as cfiAIS and IS1186 associated with the cfiA and nim gene expression. These parameters were studied in Bacteroides spp., Fusobacterium spp., Prevotella spp., Veillonella spp., Sutterella spp., and other clinical AGNB. Results: Resistance to metronidazole, clindamycin, imipenem, piperacillin–tazobactam, cefoxitin and chloramphenicol was 29%, 33.5%, 0.5%, 27.5%, 26.5% and 0%, respectively. The presence of resistance genes, viz., nim, ermF, cfiA, cepA, cfxA, was detected in 24%, 33.5%, 10%, 9.5%, 21.5% isolates, respectively. None of the tested isolates showed the presence of a cat gene and MGEs, viz., cfiAIS and IS1186. The highest resistance to all antimicrobial agents was exhibited by Bacteroides spp. The association between resistant phenotypes and genotypes was complete in clindamycin, as all clindamycin-resistant isolates showed the presence of ermF gene, and none of the susceptible strains harbored this gene; similarly, all isolates were chloramphenicol-susceptible and also lacked the cat gene, whereas the association was low among imipenem and piperacillin–tazobactam. Metronidazole and imipenem resistance was seen to be dependent on insertion sequences for the expression of AMR genes. A constrained co-existence of cepA and cfiA gene in B. fragilis species was seen. Based on the absence and presence of the cfiA gene, we divided B. fragilis into two categories, Division I (72.6%) and Division II (27.3%), respectively. Conclusion: AGNB acts as a reservoir of specific AMR genes, which may pose a threat to other anaerobes due to functional compatibility and acquisition of these genes. Thus, AST-complying standard guidelines must be performed periodically to monitor the local and institutional susceptibility trends, and rational therapeutic strategies must be adopted to direct empirical management. Full article
(This article belongs to the Special Issue Antibiotics Resistance in Gram-Negative Bacteria, 2nd Edition)
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Review

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12 pages, 607 KiB  
Review
From Species to Genes: A New Diagnostic Paradigm
by Sinead Fahy, James A. O’Connor, Roy D. Sleator and Brigid Lucey
Antibiotics 2024, 13(7), 661; https://doi.org/10.3390/antibiotics13070661 - 17 Jul 2024
Cited by 1 | Viewed by 1222
Abstract
Molecular diagnostics has the potential to revolutionise the field of clinical microbiology. Microbial identification and nomenclature have, for too long, been restricted to phenotypic characterisation. However, this species-level view fails to wholly account for genetic heterogeneity, a result of lateral gene transfer, mediated [...] Read more.
Molecular diagnostics has the potential to revolutionise the field of clinical microbiology. Microbial identification and nomenclature have, for too long, been restricted to phenotypic characterisation. However, this species-level view fails to wholly account for genetic heterogeneity, a result of lateral gene transfer, mediated primarily by mobile genetic elements. This genetic promiscuity has helped to drive virulence development, stress adaptation, and antimicrobial resistance in several important bacterial pathogens, complicating their detection and frustrating our ability to control them. We argue that, as clinical microbiologists at the front line, we must embrace the molecular technologies that allow us to focus specifically on the genetic elements that cause disease rather than the bacterial species that express them. This review focuses on the evolution of microbial taxonomy since the introduction of molecular sequencing, the role of mobile genetic elements in antimicrobial resistance, the current and emerging assays in clinical laboratories, and the comparison of phenotypic versus genotypic analyses. In essence, it is time now to refocus from species to genes as part of a new diagnostic paradigm. Full article
(This article belongs to the Special Issue Antibiotics Resistance in Gram-Negative Bacteria, 2nd Edition)
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