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Antibiotics
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Tackling Antimicrobial Resistance in Global Infectious Bacterial Pathogens
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Tackling Antimicrobial Resistance in Global Infectious Bacterial Pathogens

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

Deadline for manuscript submissions: closed (24 March 2022) | Viewed by 19852

Special Issue Editors

Prof. Dr. Sanjib Bhakta

E-Mail Website
Guest Editor
Mycobacteria Research Laboratory, Department of Biological Science, Institute of Structural and Molecular Biology, Birkbeck, University of London/UCL, Malet Street, London WC1E 7HX , UK
Interests: tuberculosis; antimicrobial drug resistance; target validation; new drug discovery; repurposing drugs
Special Issues, Collections and Topics in MDPI journals
Dr. Sam Willcocks

E-Mail Website
Guest Editor
Department of Infection Biology, The London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, UK
Interests: bacterial energy metabolism; target validation; antimicrobial resistance (AMR); infectious diseases

Special Issue Information

Dear Colleagues,

The antimicrobial resistance (AMR) crisis represents one of the great challenges of our age. While we are making progress in some areas, the truth is that globally, deaths caused by AMR bacterial infections continues to rise.

AMR is a natural process that is exacerbated by human actions. It is a multifaceted problem that requires multidisciplinary solutions at every level. We should conscientiously evaluate our practices that result in inappropriate antibiotic use, including in the agricultural and farming sectors, along with the underappreciated issue of antimicrobial pollution of our environment. These factors drive AMR, and while much focus is directed toward nosocomial infections caused by a select group of pathogens, community infections and neglected pathogens underpin a problem that permeates the quality and even the very sustainability of our current way of life.

The existing pipeline for drug discovery is economically inefficient. In particular, there are opportunities to improve the interconnectedness between academic, governmental and industrial efforts to generate new classes of antibiotics, a lofty aim that is often perceived as a high-risk investment. In this Special Issue, we highlight international research that improves our ability to brings this goal closer to reality. We share examples of the application of modern technological advances that optimize high-throughput screening approaches, novel strategies to improve the hit rates of compounds that show promise in vitro and retain activity in vivo, advances in medicinal chemical approaches to identify small-molecule inhibitors, and finally key advances in revealing new essential or virulence targets for pharmacological intervention through improved understanding of the basic biological processes that different pathogens use to cause disease, among other topics.

Prof. Dr. Sanjib Bhakta
Dr. Sam Willcocks
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

  • antimicrobial resistance
  • medicinal chemistry
  • drug discovery
  • drug repurposing
  • antibiotics
  • virulence

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Published Papers (5 papers)

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Research

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16 pages, 1161 KiB  
Article
Inactivation of Antibiotic-Resistant Bacteria in Wastewater by Ozone-Based Advanced Water Treatment Processes
by Takashi Azuma, Masaru Usui and Tetsuya Hayashi
Antibiotics 2022, 11(2), 210; https://doi.org/10.3390/antibiotics11020210 - 7 Feb 2022
Cited by 24 | Viewed by 5077
Abstract
The inactivating effect of ozone (O3)-based advanced oxidation processes (AOPs) (O3/H2O2, O3/UV, and O3/UV/H2O2 systems) on antimicrobial-resistant bacteria (AMRB) and antimicrobial-susceptible bacteria (AMSB) in sewage treatment plant (STP) [...] Read more.
The inactivating effect of ozone (O3)-based advanced oxidation processes (AOPs) (O3/H2O2, O3/UV, and O3/UV/H2O2 systems) on antimicrobial-resistant bacteria (AMRB) and antimicrobial-susceptible bacteria (AMSB) in sewage treatment plant (STP) wastewater was investigated. The AMRB were grouped into six classes: carbapenem-resistant Enterobacteriaceae (CRE), extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E), multidrug-resistant Acinetobacter (MDRA), multidrug-resistant Pseudomonas aeruginosa (MDRP), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus (VRE); these classes constituted the World Health Organization (WHO) global priority list of AMRB. The results indicate that O3-based advanced wastewater treatment inactivated all AMRB and AMSB (>99.9%) after 10 min of treatment, and significant differences (p < 0.5) were not observed in the disinfection of AMRB and AMSB by each treatment. Altered taxonomic diversity of micro-organisms based on 16S rRNA gene sequencing via O3/UV and O3/UV/H2O2 treatment showed that advanced wastewater treatments not only inactivated AMRB but also removed antimicrobial resistance genes (AMRGs) in the wastewater. Consequently, this study recommends the use of advanced wastewater treatments for treating the STP effluent, reducing environmental pollution, and alleviating the potential hazard to human health caused by AMRB, AMSB, and infectious diseases. Overall, this study provides a new method for assessing environmental risks associated with the spread of AMRB and AMSB in aquatic environments, while keeping the water environment safe and maintaining human health. Full article
(This article belongs to the Special Issue Tackling Antimicrobial Resistance in Global Infectious Bacterial Pathogens)
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12 pages, 1025 KiB  
Article
Role of AmpC-Inducing Genes in Modulating Other Serine Beta-Lactamases in Escherichia coli
by Dhriti Mallik, Diamond Jain, Sanjib Bhakta and Anindya Sundar Ghosh
Antibiotics 2022, 11(1), 67; https://doi.org/10.3390/antibiotics11010067 - 6 Jan 2022
Cited by 2 | Viewed by 2308
Abstract
The consistently mutating bacterial genotypes appear to have accelerated the global challenge with antimicrobial resistance (AMR); it is therefore timely to investigate certain less-explored fields of targeting AMR mechanisms in bacterial pathogens. One of such areas is beta-lactamase (BLA) induction that can provide [...] Read more.
The consistently mutating bacterial genotypes appear to have accelerated the global challenge with antimicrobial resistance (AMR); it is therefore timely to investigate certain less-explored fields of targeting AMR mechanisms in bacterial pathogens. One of such areas is beta-lactamase (BLA) induction that can provide us with a collection of prospective therapeutic targets. The key genes (ampD, ampE and ampG) to which the AmpC induction mechanism is linked are also involved in regulating the production of fragmented muropeptides generated during cell-wall peptidoglycan recycling. Although the involvement of these genes in inducing class C BLAs is apparent, their effect on serine beta-lactamase (serine-BLA) induction is little known. Here, by using ∆ampD and ∆ampE mutants of E. coli, we attempted to elucidate the effects of ampD and ampE on the expression of serine-BLAs originating from Enterobacteriaceae, viz., CTX-M-15, TEM-1 and OXA-2. Results show that cefotaxime is the preferred inducer for CTX-M-15 and amoxicillin for TEM-1, whereas oxacillin for OXA-2. Surprisingly, exogenous BLA expressions are elevated in ∆ampD and ∆ampE mutants but do not always alter their beta-lactam susceptibility. Moreover, the beta-lactam resistance is increased upon in trans expression of ampD, whereas the same is decreased upon ampE expression, indicating a differential effect of ampD and ampE overexpression. In a nutshell, depending on the BLA, AmpD amidase moderately facilitates a varying level of serine-BLA expression whereas AmpE transporter acts likely as a negative regulator of serine-BLA. Full article
(This article belongs to the Special Issue Tackling Antimicrobial Resistance in Global Infectious Bacterial Pathogens)
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17 pages, 6128 KiB  
Article
A Novel Use of Allopurinol as A Quorum-Sensing Inhibitor in Pseudomonas aeruginosa
by Ahmed Al Saqr, Mohammed F. Aldawsari, El-Sayed Khafagy, Moataz A. Shaldam, Wael A. H. Hegazy and Hisham A. Abbas
Antibiotics 2021, 10(11), 1385; https://doi.org/10.3390/antibiotics10111385 - 12 Nov 2021
Cited by 44 | Viewed by 3792
Abstract
Pseudomonas aeruginosa can cause a variety of healthcare-associated infections by its arsenal of virulence factors. Virulence factor production is largely controlled by the cell-to-cell communication system termed quorum sensing (QS). Targeting QS may be a good approach to inhibit the production of virulence [...] Read more.
Pseudomonas aeruginosa can cause a variety of healthcare-associated infections by its arsenal of virulence factors. Virulence factor production is largely controlled by the cell-to-cell communication system termed quorum sensing (QS). Targeting QS may be a good approach to inhibit the production of virulence factors and attenuate pathogenicity without exerting selective stress on bacterial growth. This will greatly reduce the emergence of resistant mutants. In this work, we investigated the anti-virulence and anti-QS activities of the FDA-approved drug allopurinol against the P. aeruginosa PAO1 strain. Allopurinol at 200 µg/mL (1/10 MIC) significantly decreased the production of the QS-controlled Chromobacterium violaceum CV026 violet pigment violacein and other P. aeruginosa QS-controlled virulence factors phenotypically. Furthermore, allopurinol reduced the infiltration of P. aeruginosa and leucocytes and diminished the congestion in the liver and kidney tissues of infected mice. In silico study showed that allopurinol could compete with the autoinducers on binding to the receptors LasR and RhlR by hydrogen bonding. On the molecular level, qRT-PCR proved that allopurinol showed a significant downregulating effect on all tested QS-encoding genes that regulate virulence factor production. In summary, allopurinol is a promising QS inhibitor that may be useful in the future treatment of P. aeruginosa infection. Full article
(This article belongs to the Special Issue Tackling Antimicrobial Resistance in Global Infectious Bacterial Pathogens)
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Review

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16 pages, 1831 KiB  
Review
Prevalence of Vancomycin-Resistant Enterococcus (VRE) in Poultry in Malaysia: The First Meta-Analysis and Systematic Review
by Yusuf Wada, Ahmad A. Irekeola, Rafidah H. Shueb, Mustapha Wada, Hafeez A. Afolabi, Chan Y. Yean, Azian Harun and Abdul R. Zaidah
Antibiotics 2022, 11(2), 171; https://doi.org/10.3390/antibiotics11020171 - 28 Jan 2022
Cited by 4 | Viewed by 3433
Abstract
Databases such as PubMed, Scopus and Google Scholar were searched. Data extraction and assessment of study protocol was done by two independent reviewers and the results were reviewed by a third. OpenMeta analyst and comprehensive meta-analysis (CMA) were used for the meta-analysis. The [...] Read more.
Databases such as PubMed, Scopus and Google Scholar were searched. Data extraction and assessment of study protocol was done by two independent reviewers and the results were reviewed by a third. OpenMeta analyst and comprehensive meta-analysis (CMA) were used for the meta-analysis. The random effect model was used, publication bias and between-study heterogeneity was assessed. Seventeen studies were added to the final meta-analysis. Studies were sampled from 2000–2018 and of the 8684 isolates tested, 2824 were VRE. The pooled prevalence of VRE among poultry in Malaysia was estimated at 24.0% (95% CI; 16.7–33.1%; I2 = 98.14%; p < 0.001). Between-study variability was high (t2 = 0.788; heterogeneity I2 = 98.14% with heterogeneity chi-square (Q) = 858.379, degrees of freedom (df) = 16, and p < 0.001). The funnel plot showed bias which was confirmed by Egger’s test and estimates from the leave-one-out forest plot did not affect the pooled prevalence. Pooled prevalence of VRE in chickens and ducks were 29.2% (CI = 18.8–42.5%) and 11.2%, CI = 9.0–14.0%) respectively. Enterococcus faecalis was reported most with more studies being reported in Peninsular Malaysia Central region and used antibiotic disc diffusion as detection method. Increased surveillance of VRE in poultry in Malaysia is required. Full article
(This article belongs to the Special Issue Tackling Antimicrobial Resistance in Global Infectious Bacterial Pathogens)
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12 pages, 961 KiB  
Review
Improving the Drug Development Pipeline for Mycobacteria: Modelling Antibiotic Exposure in the Hollow Fibre Infection Model
by Arundhati Maitra, Priya Solanki, Zahra Sadouki, Timothy D. McHugh and Frank Kloprogge
Antibiotics 2021, 10(12), 1515; https://doi.org/10.3390/antibiotics10121515 - 10 Dec 2021
Cited by 11 | Viewed by 4088
Abstract
Mycobacterial infections are difficult to treat, requiring a combination of drugs and lengthy treatment times, thereby presenting a substantial burden to both the patient and health services worldwide. The limited treatment options available are under threat due to the emergence of antibiotic resistance [...] Read more.
Mycobacterial infections are difficult to treat, requiring a combination of drugs and lengthy treatment times, thereby presenting a substantial burden to both the patient and health services worldwide. The limited treatment options available are under threat due to the emergence of antibiotic resistance in the pathogen, hence necessitating the development of new treatment regimens. Drug development processes are lengthy, resource intensive, and high-risk, which have contributed to market failure as demonstrated by pharmaceutical companies limiting their antimicrobial drug discovery programmes. Pre-clinical protocols evaluating treatment regimens that can mimic in vivo PK/PD attributes can underpin the drug development process. The hollow fibre infection model (HFIM) allows for the pathogen to be exposed to a single or a combination of agents at concentrations achieved in vivo–in plasma or at infection sites. Samples taken from the HFIM, depending on the analyses performed, provide information on the rate of bacterial killing and the emergence of resistance. Thereby, the HFIM is an effective means to investigate the efficacy of a drug combination. Although applicable to a wide variety of infections, the complexity of anti-mycobacterial drug discovery makes the information available from the HFIM invaluable as explored in this review. Full article
(This article belongs to the Special Issue Tackling Antimicrobial Resistance in Global Infectious Bacterial Pathogens)
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