Antimicrobial Alternatives against Antimicrobial-Resistant Pathogens

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiotic Therapy in Infectious Diseases".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 23395

Special Issue Editors


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Guest Editor
School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore, QLD 4558, Australia
Interests: microbial ecology and diversity; microbial systematics; biodiscovery; microbial biotechnology applied; environmental and industrial microbiology; marine microbiology; biological control; actinomycetology; bacteriophages
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
1. The School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen AB25 2ZD, UK
2. Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan 420008, Russia
Interests: antimicrobials; antimicrobial resistance; microbial molecular ecology; gut microbiome; omics of gut microbiome; host-microbe interaction; mucosal immunity; immune system diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Bacteria are continually evolving into antibiotic resistant strains due to their extraordinary ability to adapt to changes in their environment such as encountering antibiotics. Global efforts to create potent antibiotics are constantly thwarted by bacteria which display fascinating combat strategies to survive despite the most innovative antibiotic mechanisms. Examples include, synthesis of the enzyme penicillinase by Staphylococcus aureus to destroy the antibiotic within 6 years of its introduction. Derivative methicillin’s victory did not last long and MRSA strains developed rapidly. Although vancomycin, a glycopeptide antibiotic, successfully stopped the spread of MRSA, vancomycin-intermediate-resistant S. aureus (VISA) currently exists and the emergence of vancomycin-resistant S. aureus (VRSA) is a realistic threat for the future. There are many other examples of drug- and multidrug-resistant (MDR) bacteria and, sadly, the list is continuously growing.

The development of new antimicrobial agents, however, is not currently capable of keeping up with the growing demand for antimicrobials that are active against MDR infections. New developments could be envisaged that contribute toward acceptance and widespread use of alternative therapies that would be able to stop returning back to pre-antibiotic era where essentially any infection could be fatal.

1.1. Vaccines and Antibodies

Vaccination has been traditionally used against viral diseases. Vaccination against bacterial diseases such as tuberculosis, diphtheria, tetanus, pertussis, Haemophilus influenzae type B, cholera, typhoid, and Streptococcus pneumoniae is less common. However, the rise of AMR among pathogenic bacteria revived this field.

Antibodies are very specific in targeting certain pathogens and thus they do not disrupt commensal microbiota. Development of resistance against them is highly unlikely. However, these alternative therapeutic agents are expensive and require substantial expenditures towards infrastructure and labour cost.

1.2. Bacteriophage Therapy

This is one of the oldest forms of therapy of infectious diseases, described before the Fleming’s (1929) discovery of naturally occurring antibiotic, penicillin. The success of antibiotics in controlling bacterial infectious diseases, however, overshadowed the development of this approach and it has been largely abandoned, persisting as limited R&D and therapy options in Russia, Georgia, and Poland. The rise of AMR among bacterial pathogens, however, revived the interest in phage therapy as an alternative, which is highly specific and less damaging to commensal microbiota compared to antimicrobials.

1.3. Antimicrobial Peptides

These have long been considered as potential replacements for antimicrobials but with limited success. Synthetic peptides and synthetic membrane-active agents may bring fresh prospective to this area.

1.4. Oligonucleotide Silencing

This approach, which is in the research stage, uses oligonucleotides for silencing AMR genes. This allows re-sensitizing drug-resistant bacteria and thus reinstate some antimicrobials that lost their efficiency.

1.5. Bacteriotherapy

Various probiotics have been used for hundreds of years. Faecal transplant therapy is a relatively recent approach, which, however, has already demonstrated some success in the treatment of chronic infections such as recurrent Clostridioides difficile infections and could be potentially be useful in a number of other diseases affecting the gut and beyond.

1.6. Photodynamic Therapy

Antibacterial photodynamic therapy is increasingly recognized as having a potential to effectively kill MDR pathogenic bacteria and for low probability of resistance development, which often happens with traditional antimicrobials.

1.7. Nanoparticles

The mechanisms of antibacterial action of nanoparticles are not fully understood. It is thought that the activity is complex and may include the induction of oxidative stress, release of metal ions that are toxic to bacteria, and also non-oxidative mechanisms.

1.8. Non-killing Antimicrobials

These antimicrobials can be defined as capable of preventing the realization of the full pathogenic potential of infectious agents. They do not necessarily kill a pathogen but reduce its virulence, thus reducing damage caused to a host and allowing the immune system to clear the pathogen. These antimicrobials may target quorum sensing and other systems involved in virulence, biofilm formation, immune evasion and other pathogenic properties.

1.9. Active Components of Traditional Medicines

Although usually perceived as contrasting to scientific medicine, traditional medicine may contain substances active against infectious agents. One of the best-known examples of this kind is the identification of a potent anti-malarial drug, artemisinin, in Artemisia plants, which were used for thousands of years as a remedy for many illnesses. Antimicrobial activity may present in a number of other traditional medicines as well, and identification and characterization of these compounds may enrich our arsenal of antimicrobial alternatives.

Dr. Ipek Kurtboke

Prof. Rustam Aminov
Guest Editors

Manuscript Submission Information

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Keywords

  • Bacteriophage Therapy
  • Probiotics
  • Lantibiotics
  • Maggot Therapy
  • Bacteriotherapy
  • Bacteriophage lysins
  • Antibiotic resistance
  • “Super Bugs”

Published Papers (4 papers)

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Research

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16 pages, 3944 KiB  
Article
Flavonoids as Potential anti-MRSA Agents through Modulation of PBP2a: A Computational and Experimental Study
by Hani A. Alhadrami, Ahmed A. Hamed, Hossam M. Hassan, Lassaad Belbahri, Mostafa E. Rateb and Ahmed M. Sayed
Antibiotics 2020, 9(9), 562; https://doi.org/10.3390/antibiotics9090562 - 31 Aug 2020
Cited by 42 | Viewed by 8908
Abstract
Recently, the interest in plant-derived antimicrobial agents has increased. However, there are no sufficient studies dealing with their modes of action. Herein, we investigate an in-house library of common plant-based phenolic compounds for their potential antibacterial effects against the methicillin-resistant Staphylococcus aureus (MRSA), [...] Read more.
Recently, the interest in plant-derived antimicrobial agents has increased. However, there are no sufficient studies dealing with their modes of action. Herein, we investigate an in-house library of common plant-based phenolic compounds for their potential antibacterial effects against the methicillin-resistant Staphylococcus aureus (MRSA), a widespread life-threatening superbug. Flavonoids, which are considered major constituents in the plant kingdom, were found to be a promising class of compounds against MRSA, particularly the non-glycosylated ones. On the other hand, the glycosylated derivatives, along with the flavonolignan silibinin A, were able to restore the inhibitory activity of ampicillin against MRSA. To explore the mode of action of this class, they were subjected to an extensive inverse virtual screening (IVS), which suggested penicillin-binding protein 2a (PBP2a) as a possible target that mediates both the antibacterial and the antibiotic-synergistic effects of this class of compounds. Further molecular docking and molecular dynamic simulation experiments were conducted to support the primary IVS and the in vitro results and to study their binding modes with PBP2a. Our findings shed a light on plant-derived natural products, notably flavonoids, as a promising and readily available source for future adjuvant antimicrobial therapy against resistant strains. Full article
(This article belongs to the Special Issue Antimicrobial Alternatives against Antimicrobial-Resistant Pathogens)
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16 pages, 815 KiB  
Article
Spectrum and Antibiotic Resistance of Uropathogens in Romanian Females
by Răzvan-Cosmin Petca, Cristian Mareș, Aida Petca, Silvius Negoiță, Răzvan-Ionuț Popescu, Mihaela Boț, Enikő Barabás and Călin Bogdan Chibelean
Antibiotics 2020, 9(8), 472; https://doi.org/10.3390/antibiotics9080472 - 1 Aug 2020
Cited by 23 | Viewed by 5339
Abstract
Urinary tract infections (UTIs) in women represent a common bacteriological finding, with negligible recent and consistent research on antimicrobial resistance (AMR) in the female population. We designed a retrospective study to observe the incidence of frequent uropathogens and their resistance rates to common [...] Read more.
Urinary tract infections (UTIs) in women represent a common bacteriological finding, with negligible recent and consistent research on antimicrobial resistance (AMR) in the female population. We designed a retrospective study to observe the incidence of frequent uropathogens and their resistance rates to common antibiotics. We elaborated multicenter research in three different teaching hospitals in Romania, analyzing 13,081 urine samples, of which 1588 met the criteria of inclusion. Escherichia coli (58.37%) was the most frequent Gram-negative uropathogen, presenting high resistance rates to levofloxacin (R = 29.66%), amoxicillin–clavulanic ac. (R = 14.13%), and ceftazidime (R = 6.68%). We found good sensitivity to imipenem and meropenem (both 98.16%), amikacin (S = 96.0%), and fosfomycin (S = 90.39%). The second most prevalent uropathogen was Klebsiella (16.93%), with the highest resistance quota to amoxicillin–clavulanic ac. (R = 28.62%), levofloxacin and nitrofurantoin (both R = 15.61%), and ceftazidime (R = 15.24%), and good sensitivity to imipenem (S = 93.93%), meropenem (S = 91.91%), and amikacin (S = 88.47%). Enterococcus (13.35%) was the most encountered Gram-positive pathogen. It proved the highest resistance to levofloxacin (R = 32.07%), penicillin (R = 32.07%), and ampicillin (R = 14.62%) and good sensitivity to vancomycin (S = 91.98%), fosfomycin (S = 94.4%), and nitrofurantoin (S = 89.15%). Considering the lack of recent and consistent data on this topic, we find our survey a valuable starting research study in this area with high significance for an accurate clinical approach. Full article
(This article belongs to the Special Issue Antimicrobial Alternatives against Antimicrobial-Resistant Pathogens)
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8 pages, 187 KiB  
Article
Antibiotic Resistance in Nosocomial Bacteria Isolated from Infected Wounds of Hospitalized Patients in Czech Republic
by Milan Kolar, Pavel Cermak, Lenka Hobzova, Katerina Bogdanova, Katerina Neradova, Patrik Mlynarcik and Pavel Bostik
Antibiotics 2020, 9(6), 342; https://doi.org/10.3390/antibiotics9060342 - 18 Jun 2020
Cited by 7 | Viewed by 3203
Abstract
Hospitalized patients with wounds face an increased risk of infection with multi-drug-resistant nosocomial bacteria. In this study, samples from almost 10,000 patients from big hospitals in Czech Republic with infected wounds were analyzed for the presence of bacterial pathogens. In 7693 patients (78.8%), [...] Read more.
Hospitalized patients with wounds face an increased risk of infection with multi-drug-resistant nosocomial bacteria. In this study, samples from almost 10,000 patients from big hospitals in Czech Republic with infected wounds were analyzed for the presence of bacterial pathogens. In 7693 patients (78.8%), bacterial etiological agents were identified. Members of the Enterobacterales (37.1%) and Staphyloccus aureus (21.1%) were the most prevalent pathogens. Staphyloccus aureus showed methicillin resistance in 8.6%. Almost half of the Klebsiella pneumoniae isolates were ESBL-positive and 25.6% of the Enterobacter spp. isolates were AmpC-positive. The third most prevalent Pseudomonas aeruginosa showed resistance to 19–32% of the antipseudomonal antibiotics tested. Based on the results, amoxicillin/clavulanic acid, ampicillin/sulbactam or piperacillin/tazobactam combined with gentamicin can be recommended for antibiotic treatment of infected wounds. Once the etiological agent is identified, the therapy should be adjusted according to the species and its resistance. Full article
(This article belongs to the Special Issue Antimicrobial Alternatives against Antimicrobial-Resistant Pathogens)

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16 pages, 2745 KiB  
Review
Design and Synthesis of Small Molecules as Potent Staphylococcus aureus Sortase A Inhibitors
by Min Woo Ha, Sung Wook Yi and Seung-Mann Paek
Antibiotics 2020, 9(10), 706; https://doi.org/10.3390/antibiotics9100706 - 16 Oct 2020
Cited by 24 | Viewed by 4556
Abstract
The widespread and uncontrollable emergence of antibiotic-resistant bacteria, especially methicillin-resistant Staphylococcus aureus, has promoted a wave of efforts to discover a new generation of antibiotics that prevent or treat bacterial infections neither as bactericides nor bacteriostats. Due to its crucial role in [...] Read more.
The widespread and uncontrollable emergence of antibiotic-resistant bacteria, especially methicillin-resistant Staphylococcus aureus, has promoted a wave of efforts to discover a new generation of antibiotics that prevent or treat bacterial infections neither as bactericides nor bacteriostats. Due to its crucial role in virulence and its nonessentiality in bacterial survival, sortase A has been considered as a great target for new antibiotics. Sortase A inhibitors have emerged as promising alternative antivirulence agents against bacteria. Herein, the structural and preparative aspects of some small synthetic organic compounds that block the pathogenic action of sortase A have been described. Full article
(This article belongs to the Special Issue Antimicrobial Alternatives against Antimicrobial-Resistant Pathogens)
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