Alternative Approaches to Treating Antimicrobial Resistant Infections - 2nd Volume

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Novel Antimicrobial Agents".

Deadline for manuscript submissions: closed (1 April 2023) | Viewed by 17424

Special Issue Editors

Department of Life Sciences, University of Roehampton, London, UK
Interests: metabolic evolution; opportunistic pathogens; cystic fibrosis; Pseudomonas aeruginosa; Staphylococcus aureus
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue will focus on alternative approaches to treating antimicrobial-resistant infections. The discovery of antibiotics revolutionized the clinical treatment of bacterial infections. However, this fundamental pillar of modern medicine is now crumbling. The development of novel antimicrobials has slowed down in recent years, and major pharmaceutical firms have withdrawn from the anti-infective research area due to its low profitability.

As a consequence, many infections are now difficult to treat, which is raising the mortality and healthcare-associated costs due to difficulties in accomplishing total remission. Antimicrobial resistance is now considered one of the greatest risks to humanity. Common surgical procedures and treatments that could lead to immunosuppression may soon be considered high-risk due to the antibiotic crisis (e.g., cancer chemotherapy or organ transplants).

We are therefore inviting both reviews and original articles on the latest developments on novel antibacterial strategies to treat infections caused by antimicrobial-resistant pathogens. Topics include the development of novel combinatorial therapies based on the repurposing of anti-infectives, host-targeted therapies, bacteriophages, the use of predatory bacteria, bacteriocins, antimicrobial peptides, nanoparticles, natural compounds, immunotherapeutics, probiotics used for competitive exclusion of pathogens, and the development of novel antibacterial compounds.

Dr. Michal Letek
Dr. Volker Behrends
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

  • repurposing
  • anti-infectives
  • host-targeted therapies
  • bacteriophages
  • predatory bacteria
  • bacteriocins
  • antimicrobial peptides
  • nanoparticles
  • natural compounds
  • immunotherapy
  • probiotics
  • antibiotics

Related Special Issue

Published Papers (6 papers)

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Research

Jump to: Review

21 pages, 1896 KiB  
Article
Tobacco Seed-Based Oral Vaccination against Verocytotoxic O138 Escherichia coli as Alternative Approach to Antibiotics in Weaned Piglets
by Luciana Rossi, Matteo Dell’Anno, Lauretta Turin, Serena Reggi, Angela Lombardi, Giovanni Loris Alborali, Joel Filipe, Federica Riva, Pietro Riccaboni, Eugenio Scanziani, Paola Dall’Ara, Eugenio Demartini and Antonella Baldi
Antibiotics 2023, 12(4), 715; https://doi.org/10.3390/antibiotics12040715 - 06 Apr 2023
Cited by 1 | Viewed by 1622
Abstract
Post-weaning diarrhoea and enterotoxaemia caused by Escherichia coli are serious threats in the pig (Sus scrofa domesticus) livestock industry and are responsible for economic losses related to mortality, morbidity and stunted growth. The aim of this study was to evaluate the [...] Read more.
Post-weaning diarrhoea and enterotoxaemia caused by Escherichia coli are serious threats in the pig (Sus scrofa domesticus) livestock industry and are responsible for economic losses related to mortality, morbidity and stunted growth. The aim of this study was to evaluate the effect of an engineered tobacco seeds-based edible vaccine in O138 Escherichia coli-challenged piglets throughout a multidisciplinary approach. Thirty-six weaned piglets were enrolled and randomly divided into two experimental groups, a control (C; n = 18) group and a tobacco edible vaccination group (T, n = 18), for 29 days of trial. At days 0, 1, 2, 5 and 14, piglets of the T group were fed with 10 g of the engineered tobacco seeds line expressing F18 and VT2eB antigens, while the C group received wild-type tobacco seeds. After 20 days, 6 piglets/group were orally challenged with the Escherichia coli O138 strain (creating four subgroups: UC = unchallenged control, CC = challenged control, UT = unchallenged tobacco, CT = challenged tobacco) and fed with a high protein diet for 3 consecutive days. Zootechnical, clinical, microbiological, histological and immunological parameters were assayed and registered during the 9 days of post-challenge follow up. At 29 days post-challenge, the CT group displayed a lower average of the sum of clinical scores compared to the CC group (p < 0.05), while the CC group showed a higher average sum of the faecal score (diarrhoea) (p < 0.05) than the CT group. A decreased number of days of shedding of the pathogenic strain was observed in the CT compared to the CC group (p < 0.05). Specific anti-F18 IgA molecules were significantly higher in the CT group compared to the CC group’s faecal samples during the post-challenge period (p < 0.01). In conclusion, edible vaccination with engineered tobacco seeds showed a protective effect on clinical symptoms and diarrhoea incidence during the post-challenge period, characterized by a limited time of pathogenic strain shedding in faeces. Full article
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15 pages, 2779 KiB  
Article
Combination of Meropenem and Zinc Oxide Nanoparticles; Antimicrobial Synergism, Exaggerated Antibiofilm Activity, and Efficient Therapeutic Strategy against Bacterial Keratitis
by Mohamed El-Telbany, Alzhraa Ali Mohamed, Galal Yahya, Aliaa Abdelghafar, Mahmoud Saad Abdel-Halim, Sameh Saber, Mohamed A. Alfaleh, Asmaa H. Mohamed, Fatma Abdelrahman, Hoda A. Fathey, Gehad H. Ali and Mohamed Abdel-Haleem
Antibiotics 2022, 11(10), 1374; https://doi.org/10.3390/antibiotics11101374 - 07 Oct 2022
Cited by 15 | Viewed by 2227
Abstract
Pseudomonas aeruginosa is an opportunistic gram-negative human pathogen that causes a wide range of infections, including nosocomial infections. Aside from the intrinsic and acquired antimicrobial resistance against many classes of antibiotics, P. aeruginosa can produce an extracellular polymeric matrix called “biofilm” that protects [...] Read more.
Pseudomonas aeruginosa is an opportunistic gram-negative human pathogen that causes a wide range of infections, including nosocomial infections. Aside from the intrinsic and acquired antimicrobial resistance against many classes of antibiotics, P. aeruginosa can produce an extracellular polymeric matrix called “biofilm” that protects bacteria from antibiotics and harmful factors. Biofilm enables P. aeruginosa to develop chronic infections. This study assessed the inhibitory action of ZnO-nanoparticles against biofilms formed by multidrug-resistant P. aeruginosa strains. A collection of 24 clinical strains of P. aeruginosa were tested for their antimicrobial resistance against different antibiotics using the disk diffusion method. The antibiofilm activity of ZnO-NPs was assessed using the microtiter plate biofilm assay. The application of ZnO-NPs dramatically modulated the resistance profile and biofilm activity of P. aeruginosa. The combination of ZnO-NPs and meropenem showed synergistic antipseudomonal activity with lower MICs. The scanning electron microscope (SEM) micrographs revealed complete inhibition of biofilms treated with the meropenem–ZnO-NPs combination. Reduced expression of biofilm regulating genes lasR, pslA, and fliC was detected, reflecting the enhanced antibiofilm effect of ZnO-NPs. In vivo application of this antimicrobial mixture completely cured P. aeruginosa-induced keratitis in rats. Our findings represent a dual enhancement of antibacterial and antibiofilm activity via the use of meropenem–ZnO-NPs combination against carbapenem-resistant P. aeruginosa infections. Full article
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17 pages, 881 KiB  
Article
Silver Nanoparticle-Based Combinations with Antimicrobial Agents against Antimicrobial-Resistant Clinical Isolates
by Areej M. Alotaibi, Nasser B. Alsaleh, Alanoud T. Aljasham, Essam A. Tawfik, Mohammed M. Almutairi, Mohammed A. Assiri, Musaed Alkholief and Mashal M. Almutairi
Antibiotics 2022, 11(9), 1219; https://doi.org/10.3390/antibiotics11091219 - 08 Sep 2022
Cited by 17 | Viewed by 2706
Abstract
The increasing prevalence of antimicrobial-resistant (AMR) bacteria along with the limited development of antimicrobials warrant investigating novel antimicrobial modalities. Emerging inorganic engineered nanomaterials (ENMs), most notably silver nanoparticles (AgNPs), have demonstrated superior antimicrobial properties. However, AgNPs, particularly those of small size, could exert [...] Read more.
The increasing prevalence of antimicrobial-resistant (AMR) bacteria along with the limited development of antimicrobials warrant investigating novel antimicrobial modalities. Emerging inorganic engineered nanomaterials (ENMs), most notably silver nanoparticles (AgNPs), have demonstrated superior antimicrobial properties. However, AgNPs, particularly those of small size, could exert overt toxicity to mammalian cells. This study investigated whether combining AgNPs and conventional antimicrobials would produce a synergistic response and determined the optimal and safe minimum inhibitory concentration (MIC) range against several wild-type Gram-positive and -negative strains and three different clinical isolates of AMR Klebsiella pneumoniae. Furthermore, the cytotoxicity of the synergistic combinations was assessed in a human hepatocyte model. The results showed that the AgNPs (15–25 nm) were effective against Gram-negative bacteria (MIC of 16–128 µg/mL) but not Gram-positive strains (MIC of 256 µg/mL). Both wild-type and AMR K. pneumoniae had similar MIC values following exposure to AgNPs. Importantly, co-exposure to combinations of AgNPs and antimicrobial agents, including kanamycin, colistin, rifampicin, and vancomycin, displayed synergy against both wild-type and AMR K. pneumoniae isolates (except for vancomycin against AMR strain I). Notably, the tested combinations demonstrated no to minimal toxicity against hepatocytes. Altogether, this study indicates the potential of combining AgNPs with conventional antimicrobials to overcome AMR bacteria. Full article
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14 pages, 4388 KiB  
Article
Antivirulence Agent as an Adjuvant of β-Lactam Antibiotics in Treating Staphylococcal Infections
by Peng Gao, Yuanxin Wei, Sherlock Shing Chiu Tai, Pradeep Halebeedu Prakash, Ho Ting Venice Iu, Yongli Li, Hin Cheung Bill Yam, Jonathan Hon Kwan Chen, Pak Leung Ho, Julian Davies and Richard Yi Tsun Kao
Antibiotics 2022, 11(6), 819; https://doi.org/10.3390/antibiotics11060819 - 17 Jun 2022
Cited by 3 | Viewed by 2038
Abstract
Staphylococcus aureus can cause a plethora of life-threatening infections. Antibiotics have been extensively used to treat S. aureus infections. However, when antibiotics are used at sub-inhibitory concentrations, especially for β-lactam antibiotics, they may enhance staphylococcal pathogenicity and exacerbate the infection. The combination of [...] Read more.
Staphylococcus aureus can cause a plethora of life-threatening infections. Antibiotics have been extensively used to treat S. aureus infections. However, when antibiotics are used at sub-inhibitory concentrations, especially for β-lactam antibiotics, they may enhance staphylococcal pathogenicity and exacerbate the infection. The combination of antivirulence agents and antibiotics may be a novel approach to controlling antibiotic-induced S. aureus pathogenicity. We have illustrated that under in vitro conditions, antivirulence agent M21, when administered concurrently with ampicillin, suppressed the expression and production of virulence factors induced by ampicillin. In a mouse peritonitis model, M21 reduced bacterial load irrespective of administration of ampicillin. In a bacteremia model, combinatorial treatment consisting of ampicillin or ceftazidime and M21 increased the survival rate of mice and reduced cytokine abundance, suggesting the suppression of antibiotic-induced virulence by M21. Different from traditional antibiotic adjuvants, an antivirulence agent may not synergistically inhibit bacterial growth in vitro, but effectively benefit the host in vivo. Collectively, our findings from this study demonstrated the benefits of antivirulence–antibiotic combinatorial treatment against S. aureus infections and provide a new perspective on the development of antibiotic adjuvants. Full article
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Review

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14 pages, 1226 KiB  
Review
Nickel Nanoparticles: Applications and Antimicrobial Role against Methicillin-Resistant Staphylococcus aureus Infections
by Elham Zarenezhad, Hussein T. Abdulabbas, Mahrokh Marzi, Esraa Ghazy, Mohammad Ekrahi, Babak Pezeshki, Abdolmajid Ghasemian and Amira A. Moawad
Antibiotics 2022, 11(9), 1208; https://doi.org/10.3390/antibiotics11091208 - 07 Sep 2022
Cited by 17 | Viewed by 3543
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) has evolved vast antibiotic resistance. These strains contain numerous virulence factors facilitating the development of severe infections. Considering the costs, side effects, and time duration needed for the synthesis of novel drugs, seeking efficient alternative approaches for the eradication [...] Read more.
Methicillin-resistant Staphylococcus aureus (MRSA) has evolved vast antibiotic resistance. These strains contain numerous virulence factors facilitating the development of severe infections. Considering the costs, side effects, and time duration needed for the synthesis of novel drugs, seeking efficient alternative approaches for the eradication of drug-resistant bacterial agents seems to be an unmet requirement. Nickel nanoparticles (NiNPs) have been applied as prognostic and therapeutic cheap agents to various aspects of biomedical sciences. Their antibacterial effects are exerted via the disruption of the cell membrane, the deformation of proteins, and the inhibition of DNA replication. NiNPs proper traits include high-level chemical stability and binding affinity, ferromagnetic properties, ecofriendliness, and cost-effectiveness. They have outlined pleomorphic and cubic structures. The combined application of NiNPs with CuO, ZnO, and CdO has enhanced their anti-MRSA effects. The NiNPs at an approximate size of around 50 nm have exerted efficient anti-MRSA effects, particularly at higher concentrations. NiNPs have conferred higher antibacterial effects against MRSA than other nosocomial bacterial pathogens. The application of green synthesis and low-cost materials such as albumin and chitosan enhance the efficacy of NPs for therapeutic purposes. Full article
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21 pages, 3027 KiB  
Review
Nanozybiotics: Nanozyme-Based Antibacterials against Bacterial Resistance
by Caiyu Zhou, Qian Wang, Jing Jiang and Lizeng Gao
Antibiotics 2022, 11(3), 390; https://doi.org/10.3390/antibiotics11030390 - 15 Mar 2022
Cited by 24 | Viewed by 4429
Abstract
Infectious diseases caused by bacteria represent a global threat to human health. However, due to the abuse of antibiotics, drug-resistant bacteria have evolved rapidly and led to the failure of antibiotics treatment. Alternative antimicrobial strategies different to traditional antibiotics are urgently needed. Enzyme-based [...] Read more.
Infectious diseases caused by bacteria represent a global threat to human health. However, due to the abuse of antibiotics, drug-resistant bacteria have evolved rapidly and led to the failure of antibiotics treatment. Alternative antimicrobial strategies different to traditional antibiotics are urgently needed. Enzyme-based antibacterials (Enzybiotics) have gradually attracted interest owing to their advantages including high specificity, rapid mode-of-action, no resistance development, etc. However, due to their low stability, potential immunogenicity, and high cost of natural enzymes, enzybiotics have limitations in practical antibacterial therapy. In recent years, many nanomaterials with enzyme-like activities (Nanozymes) have been discovered as a new generation of artificial enzymes and perform catalytic antibacterial effects against bacterial resistance. To highlight the progress in this field of nanozyme-based antibacterials (Nanozybiotics), this review discussed the antibacterial mechanism of action of nanozybiotics with a comparison with enzybiotics. We propose that nanozybiotics may bear promising applications in antibacterial therapy, due to their high stability, rapid bacterial killing, biofilm elimination, and low cost. Full article
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