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Microorganisms
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Breaking the Code of Antibiotic Resistance
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Breaking the Code of Antibiotic Resistance

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Antimicrobial Agents and Resistance".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 23412

Special Issue Editors

Prof. Dr. Henrietta Venter

E-Mail Website
Guest Editor
School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia
Interests: antimicrobial resistance; drug efflux proteins; novel antibiotics; mechanisms of resistance; multidrug resistance
Special Issues, Collections and Topics in MDPI journals
Dr. Liping Li

E-Mail Website
Guest Editor
Department of Molecular Sciences, Macquarie University, North Ryde, NSW, Australia
Interests: antimicrobial resistance; drug efflux pumps; functional genomics; transcriptomics

Special Issue Information

Dear Colleagues,

Antimicrobial resistance is one of the most serious threats facing society today. Without urgent action, we are heading for a post-antibiotic era, where minor injuries will be fatal, and many medical procedures will no longer be feasible. To facilitate new antimicrobial drug discovery as well as to hamper the development and dissemination of resistance, a better understanding of the mechanisms of drug resistance is essential. In this Special Issue, we invite you to submit a review or original research article on a topic that would contribute to our understanding of antimicrobial resistance mechanisms, and would provide insight into how to prevent the development and dissemination of antimicrobial resistant microorganisms.

Prof. Dr. Henrietta Venter
Dr. Liping Li
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. Microorganisms 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 2700 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

  • antimicrobial resistance
  • resistance mechanism
  • antibiotic
  • resistance gene
  • resistance breaker
  • resistance factors

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Published Papers (6 papers)

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Research

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20 pages, 3194 KiB  
Article
Repurposing of the Fasciolicide Triclabendazole to Treat Infections Caused by Staphylococcus spp. and Vancomycin-Resistant Enterococci
by Hongfei Pi, Abiodun D. Ogunniyi, Bhumi Savaliya, Hang Thi Nguyen, Stephen W. Page, Ernest Lacey, Henrietta Venter and Darren J. Trott
Microorganisms 2021, 9(8), 1697; https://doi.org/10.3390/microorganisms9081697 - 10 Aug 2021
Cited by 6 | Viewed by 3027
Abstract
One approach to combat the increasing incidence of multidrug-resistant (MDR) bacterial pathogens involves repurposing existing compounds with known safety and development pathways as new antibacterial classes with potentially novel mechanisms of action. Here, triclabendazole (TCBZ), a drug originally developed to treat Fasciola hepatica [...] Read more.
One approach to combat the increasing incidence of multidrug-resistant (MDR) bacterial pathogens involves repurposing existing compounds with known safety and development pathways as new antibacterial classes with potentially novel mechanisms of action. Here, triclabendazole (TCBZ), a drug originally developed to treat Fasciola hepatica (liver fluke) in sheep and cattle, and later in humans, was evaluated as an antibacterial alone or in combination with sub-inhibitory concentrations of polymyxin B (PMB) against clinical isolates and reference strains of key Gram-positive and Gram-negative bacteria. We show for the first time that in vitro, TCBZ selectively kills methicillin-sensitive and methicillin-resistant Staphylococcus aureus and Staphylococcus pseudintermedius at a minimum inhibitory concentration (MIC) range of 2–4 µg/mL, and vancomycin-resistant enterococci at a MIC range of 4–8 µg/mL. TCBZ also inhibited key Gram-negative bacteria in the presence of sub-inhibitory concentrations of PMB, returning MIC90 values of 1 µg/mL for Escherichia coli, 8 µg/mL for Klebsiella pneumoniae, 2 µg/mL for Acinetobacter baumannii and 4 µg/mL for Pseudomonasaeruginosa. Interestingly, TCBZ was found to be bacteriostatic against intracellular S. aureus but bactericidal against intracellular S. pseudintermedius. Additionally, TCBZ’s favourable pharmacokinetic (PK) and pharmacodynamic (PD) profile was further explored by in vivo safety and efficacy studies using a bioluminescent mouse model of S. aureus sepsis. We show that repeated four-hourly oral treatment of mice with 50 mg/kg TCBZ after systemic S. aureus challenge resulted in a significant reduction in S. aureus populations in the blood to 18 h post-infection (compared to untreated mice) but did not clear the bacterial infection from the bloodstream, consistent with in vivo bacteriostatic activity. These results indicate that additional pharmaceutical development of TCBZ may enhance its PK/PD, allowing it to be an appropriate candidate for the treatment of serious MDR bacterial pathogens. Full article
(This article belongs to the Special Issue Breaking the Code of Antibiotic Resistance)
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11 pages, 1568 KiB  
Article
Analysis of 56,348 Genomes Identifies the Relationship between Antibiotic and Metal Resistance and the Spread of Multidrug-Resistant Non-Typhoidal Salmonella
by Gavin J. Fenske and Joy Scaria
Microorganisms 2021, 9(7), 1468; https://doi.org/10.3390/microorganisms9071468 - 9 Jul 2021
Cited by 4 | Viewed by 2542
Abstract
Salmonella enterica is common foodborne pathogen that generates both enteric and systemic infections in hosts. Antibiotic resistance is common is certain serovars of the pathogen and of great concern to public health. Recent reports have documented the co-occurrence of metal resistance with antibiotic [...] Read more.
Salmonella enterica is common foodborne pathogen that generates both enteric and systemic infections in hosts. Antibiotic resistance is common is certain serovars of the pathogen and of great concern to public health. Recent reports have documented the co-occurrence of metal resistance with antibiotic resistance in one serovar of S. enterica. Therefore, we sought to identify possible co-occurrence in a large genomic dataset. Genome assemblies of 56,348 strains of S. enterica comprising 20 major serovars were downloaded from NCBI. The downloaded assemblies were quality controlled and in silico serotyped to ensure consistency and avoid improper annotation from public databases. Metal and antibiotic resistance genes were identified in the genomes as well as plasmid replicons. Co-occurrent genes were identified by constructing a co-occurrence matrix and grouping said matrix using k-means clustering. Three groups of co-occurrent genes were identified using k-means clustering. Group 1 was comprised of the pco and sil operons that confer resistance to copper and silver, respectively. Group 1 was distributed across four serovars. Group 2 contained the majority of the genes and little to no co-occurrence was observed. Metal and antibiotic co-occurrence was identified in group 3 that contained genes conferring resistance to: arsenic, mercury, beta-lactams, sulfonamides, and tetracyclines. Group 3 genes were also associated with an IncQ1 class plasmid replicon. Metal and antibiotic co-occurrence from group 3 genes is mostly isolated to one clade of S. enterica I 4,[5],12:i:-. Full article
(This article belongs to the Special Issue Breaking the Code of Antibiotic Resistance)
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17 pages, 1150 KiB  
Article
First Emergence of Resistance to Macrolides and Tetracycline Identified in Mannheimia haemolytica and Pasteurella multocida Isolates from Beef Feedlots in Australia
by Tamara Alhamami, Piklu Roy Chowdhury, Nancy Gomes, Mandi Carr, Tania Veltman, Manouchehr Khazandi, Joanne Mollinger, Ania T. Deutscher, Conny Turni, Layla Mahdi, Henrietta Venter, Sam Abraham, Steven P. Djordjevic and Darren J. Trott
Microorganisms 2021, 9(6), 1322; https://doi.org/10.3390/microorganisms9061322 - 17 Jun 2021
Cited by 13 | Viewed by 4454 | Correction
Abstract
Bovine respiratory disease (BRD) causes high morbidity and mortality in beef cattle worldwide. Antimicrobial resistance (AMR) monitoring of BRD pathogens is critical to promote appropriate antimicrobial stewardship in veterinary medicine for optimal treatment and control. Here, the susceptibility of Mannheimia haemolytica and Pasteurella [...] Read more.
Bovine respiratory disease (BRD) causes high morbidity and mortality in beef cattle worldwide. Antimicrobial resistance (AMR) monitoring of BRD pathogens is critical to promote appropriate antimicrobial stewardship in veterinary medicine for optimal treatment and control. Here, the susceptibility of Mannheimia haemolytica and Pasteurella multicoda isolates obtained from BRD clinical cases (deep lung swabs at post-mortem) among feedlots in four Australian states (2014–2019) was determined for 19 antimicrobial agents. The M. haemolytica isolates were pan-susceptible to all tested agents apart from a single macrolide-resistant isolate (1/88; 1.1%) from New South Wales (NSW). Much higher frequencies of P. multocida isolates were resistant to tetracycline (18/140; 12.9%), tilmicosin (19/140; 13.6%), tulathromycin/gamithromycin (17/140; 12.1%), and ampicillin/penicillin (6/140; 4.6%). Five P. multocida isolates (3.6%), all obtained from NSW in 2019, exhibited dual resistance to macrolides and tetracycline, and a further two Queensland isolates from 2019 (1.4%) exhibited a multidrug-resistant phenotype to ampicillin/penicillin, tetracycline, and tilmicosin. Random-amplified polymorphic DNA (RAPD) typing identified a high degree of genetic homogeneity among the M. haemolytica isolates, whereas P. multocida isolates were more heterogeneous. Illumina whole genome sequencing identified the genes msr(E) and mph(E)encoding macrolide resistance, tet(R)-tet(H) or tet(Y) encoding tetracycline resistance, and blaROB-1 encoding ampicillin/penicillin resistance in all isolates exhibiting a corresponding resistant phenotype. The exception was the tilmicosin-resistant, tulathromycin/gamithromycin-susceptible phenotype identified in two Queensland isolates, the genetic basis of which could not be determined. These results confirm the first emergence of AMR in M. haemolytica and P. multocida from BRD cases in Australia, which should be closely monitored. Full article
(This article belongs to the Special Issue Breaking the Code of Antibiotic Resistance)
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18 pages, 2547 KiB  
Article
Efflux Pump-Driven Antibiotic and Biocide Cross-Resistance in Pseudomonas aeruginosa Isolated from Different Ecological Niches: A Case Study in the Development of Multidrug Resistance in Environmental Hotspots
by Anteneh Amsalu, Sylvia A. Sapula, Miguel De Barros Lopes, Bradley J. Hart, Anh H. Nguyen, Barbara Drigo, John Turnidge, Lex EX Leong and Henrietta Venter
Microorganisms 2020, 8(11), 1647; https://doi.org/10.3390/microorganisms8111647 - 24 Oct 2020
Cited by 68 | Viewed by 6984
Abstract
Pseudomonas aeruginosa is an opportunistic pathogen displaying high intrinsic antimicrobial resistance and the ability to thrive in different ecological environments. In this study, the ability of P. aeruginosa to develop simultaneous resistance to multiple antibiotics and disinfectants in different natural niches were investigated [...] Read more.
Pseudomonas aeruginosa is an opportunistic pathogen displaying high intrinsic antimicrobial resistance and the ability to thrive in different ecological environments. In this study, the ability of P. aeruginosa to develop simultaneous resistance to multiple antibiotics and disinfectants in different natural niches were investigated using strains collected from clinical samples, veterinary samples, and wastewater. The correlation between biocide and antimicrobial resistance was determined by employing principal component analysis. Molecular mechanisms linking biocide and antimicrobial resistance were interrogated by determining gene expression using RT-qPCR and identifying a potential genetic determinant for co- and cross-resistance using whole-genome sequencing. A subpopulation of P. aeruginosa isolates belonging to three sequence types was resistant against the common preservative benzalkonium chloride and showed cross-resistance to fluoroquinolones, cephalosporins, aminoglycosides, and multidrug resistance. Of these, the epidemiological high-risk ST235 clone was the most abundant. The overexpression of the MexAB-OprM drug efflux pump resulting from amino acid mutations in regulators MexR, NalC, or NalD was the major contributing factor for cross-resistance that could be reversed by an efflux pump inhibitor. This is the first comparison of antibiotic-biocide cross-resistance in samples isolated from different ecological niches and serves as a confirmation of laboratory-based studies on biocide adapted isolates. The isolates from wastewater had a higher incidence of multidrug resistance and biocide-antibiotic cross-resistance than those from clinical and veterinary settings. Full article
(This article belongs to the Special Issue Breaking the Code of Antibiotic Resistance)
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11 pages, 1579 KiB  
Article
Long-Term Surveillance of Antibiotic Prescriptions and the Prevalence of Antimicrobial Resistance in Non-Fermenting Gram-Negative Bacilli
by Chia-Huei Chou, Yi-Ru Lai, Chih-Yu Chi, Mao-Wang Ho, Chao-Ling Chen, Wei-Chih Liao, Cheng-Mao Ho, Yu-An Chen, Chih-Yu Chen, Yu-Tzu Lin, Chia-Der Lin and Chih-Ho Lai
Microorganisms 2020, 8(3), 397; https://doi.org/10.3390/microorganisms8030397 - 12 Mar 2020
Cited by 11 | Viewed by 3692
Abstract
The increasing emergence of multidrug-resistant (MDR) bacteria has been recognized as a public health threat worldwide. Hospitalized patients and outpatients are commonly infected by non-fermenting Gram-negative bacilli (NFGNB), particularly the Acinetobacter calcoaceticus-Acinetobacter baumannii complex (ACB) and Pseudomonas aeruginosa. Antimicrobial agents [...] Read more.
The increasing emergence of multidrug-resistant (MDR) bacteria has been recognized as a public health threat worldwide. Hospitalized patients and outpatients are commonly infected by non-fermenting Gram-negative bacilli (NFGNB), particularly the Acinetobacter calcoaceticus-Acinetobacter baumannii complex (ACB) and Pseudomonas aeruginosa. Antimicrobial agents are critical for treating the nosocomial infections caused by NFGNB. The aim of this study was to assess antimicrobial resistance and the use of antimicrobial agents. The bacterial isolates of 638,152 specimens from both inpatients and outpatients, retrieved from 2001 to 2008 at a medical center in central Taiwan, were examined for their susceptibility to various antimicrobial agents, including cefepime, imipenem, ciprofloxacin, gentamicin, amikacin, meropenem, and levofloxacin. Administrated prescriptions of the monitored antibiotics were analyzed using the Taiwan National Health Insurance Research Database (NHIRD). Our results show that the defined daily doses (DDDs) for cefepime, imipenem, and ciprofloxacin increased with time, and a trend toward reduced antimicrobial sensitivities of both ACB and P. aeruginosa was noticeable. In conclusion, the antimicrobial sensitivities of ACB and P. aeruginosa were reduced with the increased use of antibiotics. Continuous surveillance of antibiotic prescriptions and the prevalence of emerging resistance in nosocomial infections is warranted. Full article
(This article belongs to the Special Issue Breaking the Code of Antibiotic Resistance)
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2 pages, 184 KiB  
Correction
Correction: Alhamami et al. First Emergence of Resistance to Macrolides and Tetracycline Identified in Mannheimia haemolytica and Pasteurella multocida Isolates from Beef Feedlots in Australia. Microorganisms 2021, 9, 1322
by Tamara Alhamami, Piklu Roy Chowdhury, Nancy Gomes, Mandi Carr, Tania Veltman, Manouchehr Khazandi, Joanne Mollinger, Ania T. Deutscher, Conny Turni, Layla Mahdi, Henrietta Venter, Sam Abraham, Steven P. Djordjevic and Darren J. Trott
Microorganisms 2022, 10(4), 825; https://doi.org/10.3390/microorganisms10040825 - 15 Apr 2022
Cited by 1 | Viewed by 1586
Abstract
The authors wish to make the following corrections to this paper [...] Full article
(This article belongs to the Special Issue Breaking the Code of Antibiotic Resistance)
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