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Tackling New and Reemerging Infectious Diseases through the Development of Novel Anti-infectives

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (15 June 2023) | Viewed by 21215

Special Issue Editors

Dr. Clemente Capasso

E-Mail Website
Guest Editor
Institute of Bioscience and Bioresources (IBBR), National Research Council, Via Pietro Castellino 111, 80131 Napoli, Italy
Interests: protein biochemistry; recombinant protein; heterologous expression; carbonic anhydrase; enzyme and protein purification; enzyme characterization; enzyme thermostability; cold-adapted enzymes
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Claudiu T. Supuran

grade E-Mail Website
Guest Editor
Neurofarba Department, Section of Farmaceutical and Neutraceutical Sciences, University of Florence, Sesto Fiorentino, 50019 Florence, Italy
Interests: drug design; metalloenzymes; carbonic anhydrases; anticancer agents; antiinfectives; sulfonamides; coumarins
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The multiple challenges to the endemic, epidemic, and pandemic of infectious diseases call for a worldwide, systematic approach to quickening the efforts to discover pharmacological agents against new and reemerging infectious diseases. For example, no specific drugs are currently available to treat COVID-19, resulting in many associated morbidities and deaths frequently recorded, mostly among elderly patients affected by chronic pathologies. Although vaccines for Covid-19 are available, the urgency to identify effective drugs (i.e., antivirals) remains as, on a large scale, immunization reaches its effectiveness outside the time frame allowed to handle a potentially catastrophic pandemic. Moreover, antiviral drugs' association with vaccines represents an ideal pharmacological strategy to control the viral spread. Contagious diseases caused by viruses and resistant bacteria represent a growing global health risk across public health concerns mainly because infections are believed to occur with increasing frequency and importance, with expansions in global population, travel, climate change, and geopolitical threats. The characterization of pathogen biology, pathogenesis, and host-response genomic pathways across multiple infectious agents, offers the possibility to find new targets of interventions (e.g., crucial enzymes), which serve as broad-spectrum drug targets. They can be modulated by novel or repurposed therapeutic modalities and will similarly impact numerous pathogens. Of course, the decline in the number of new drugs being approved, combined with an economically unsustainable rise in costs, representing the pharmaceutical industry's paradox in the pharmaceutical industry, should be solved.

Prof. Dr. Clemente Capasso
Prof. Dr. Claudiu T. Supuran
Guest Editors

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Keywords

  • antivirals
  • antibacterials
  • virus
  • CoViD-19
  • pathogenic bacteria
  • antibiotic resistance
  • antifungals
  • anthelmintics
  • antimalarials
  • antiprotozoals

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Published Papers (5 papers)

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Research

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19 pages, 3545 KiB  
Article
Combating Black Fungus: Using Allicin as a Potent Antifungal Agent against Mucorales
by Christina Schier, Martin C. H. Gruhlke, Georg Reucher, Alan J. Slusarenko and Lothar Rink
Int. J. Mol. Sci. 2023, 24(24), 17519; https://doi.org/10.3390/ijms242417519 - 15 Dec 2023
Cited by 1 | Viewed by 1847
Abstract
Invasive fungal (IF) diseases are a leading global cause of mortality, particularly among immunocompromised individuals. The SARS-CoV-2 pandemic further exacerbated this scenario, intensifying comorbid IF infections such as mucormycoses of the nasopharynx. In the work reported here, it is shown that zygomycetes, significant [...] Read more.
Invasive fungal (IF) diseases are a leading global cause of mortality, particularly among immunocompromised individuals. The SARS-CoV-2 pandemic further exacerbated this scenario, intensifying comorbid IF infections such as mucormycoses of the nasopharynx. In the work reported here, it is shown that zygomycetes, significant contributors to mycoses, are sensitive to the natural product allicin. Inhibition of Mucorales fungi by allicin in solution and by allicin vapor was demonstrated. Mathematical modeling showed that the efficacy of allicin vapor is comparable to direct contact with the commercially available antifungal agent amphotericin B (ampB). Furthermore, the study revealed a synergistic interaction between allicin and the non-volatile ampB. The toxicity of allicin solution to human cell lines was evaluated and it was found that the half maximal effective concentration (EC50) of allicin was 25–72 times higher in the cell lines as compared to the fungal spores. Fungal allicin sensitivity depends on the spore concentration, as demonstrated in a drop test. This study shows the potential of allicin, a sulfur-containing defense compound from garlic, to combat zygomycete fungi. The findings underscore allicin’s promise for applications in infections of the nasopharynx via inhalation, suggesting a novel therapeutic avenue against challenging fungal infections. Full article
(This article belongs to the Special Issue Tackling New and Reemerging Infectious Diseases through the Development of Novel Anti-infectives)
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12 pages, 2227 KiB  
Article
May Sulfonamide Inhibitors of Carbonic Anhydrases from Mammaliicoccus sciuri Prevent Antimicrobial Resistance Due to Gene Transfer to Other Harmful Staphylococci?
by Viviana De Luca, Simone Giovannuzzi, Claudiu T. Supuran and Clemente Capasso
Int. J. Mol. Sci. 2022, 23(22), 13827; https://doi.org/10.3390/ijms232213827 - 10 Nov 2022
Cited by 14 | Viewed by 1947
Abstract
Mammaliicoccus sciuri, previously known as Staphylococcus sciuri, is a Gram-positive bacterium involved in gene transfer phenomena that confer resistance to multiple antibiotics. These plasmid-encoded genes can be easily transferred to other pathogenic staphylococci. Because antibiotic resistance is rising, inhibiting M. sciuri [...] Read more.
Mammaliicoccus sciuri, previously known as Staphylococcus sciuri, is a Gram-positive bacterium involved in gene transfer phenomena that confer resistance to multiple antibiotics. These plasmid-encoded genes can be easily transferred to other pathogenic staphylococci. Because antibiotic resistance is rising, inhibiting M. sciuri proliferation may be a credible strategy for restricting antimicrobial resistance gene transfer to other pathogenic bacteria. Recently, it has been shown that blocking bacterial carbonic anhydrases (CAs, EC 4.2.1.1), metalloenzymes sustaining bacterial metabolic activities, can reduce pathogen survival and fitness. Here, the recombinant M. sciuri γ-CA (MscCAγ) has been cloned and purified, utilizing the DNA recombinant technology. Its kinetic properties for the CO2 hydration reaction, as well as the sulfonamide inhibition profile, were investigated and compared with those reported earlier for MscCAβ (previously described as SauBCA) and the two off-target human CA isoforms (hCA I and hCA II). The recombinant MscCAγ showed significant hydratase activity. Moreover, the MscCAγ sulfonamide inhibitory profile was different from that of MscCAβ, implying that a varied amino acid set typifies the catalytic pocket of the two enzymes. These differences provide additional evidence for the possibility of developing novel CA class-specific inhibitors. Full article
(This article belongs to the Special Issue Tackling New and Reemerging Infectious Diseases through the Development of Novel Anti-infectives)
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18 pages, 3862 KiB  
Article
A Strategy for the Rapid Development of a Safe Vibrio cholerae Candidate Vaccine Strain
by Dmitry S. Karpov, Anna V. Goncharenko, Evgenii V. Usachev, Daria V. Vasina, Elizaveta V. Divisenko, Yaroslava M. Chalenko, Andrei A. Pochtovyi, Roman S. Ovchinnikov, Valentin V. Makarov, Sergei M. Yudin, Artem P. Tkachuk and Vladimir A. Gushchin
Int. J. Mol. Sci. 2021, 22(21), 11657; https://doi.org/10.3390/ijms222111657 - 28 Oct 2021
Cited by 3 | Viewed by 2849
Abstract
Approximately 1/6 of humanity is at high risk of experiencing cholera epidemics. The development of effective and safe vaccines against Vibrio cholerae, the primary cause of cholera, is part of the public health measures to prevent cholera epidemics. Natural nontoxigenic V. cholerae isolates [...] Read more.
Approximately 1/6 of humanity is at high risk of experiencing cholera epidemics. The development of effective and safe vaccines against Vibrio cholerae, the primary cause of cholera, is part of the public health measures to prevent cholera epidemics. Natural nontoxigenic V. cholerae isolates represent a source of new genetically improved and relatively safe vaccine strains. However, the genomic engineering of wild-type V. cholerae strains is difficult, and these strains are genetically unstable due to their high homologous recombination activity. We comprehensively characterized two V. cholerae isolates using genome sequencing, bioinformatic analysis, and microscopic, physiological, and biochemical tests. Genetic constructs were Gibson assembled and electrotransformed into V. cholerae. Bacterial colonies were assessed using standard microbiological and immunological techniques. As a result, we created a synthetic chromoprotein-expressing reporter operon. This operon was used to improve the V. cholerae genome engineering approach and monitor the stability of the genetic constructs. Finally, we created a stable candidate V. cholerae vaccine strain bearing a recA deletion and expressing the β-subunit of cholera toxin. Thus, we developed a strategy for the rapid creation of genetically stable and relatively safe candidate vaccine strains. This strategy can be applied not only to V. cholerae but also to other important human bacterial pathogens. Full article
(This article belongs to the Special Issue Tackling New and Reemerging Infectious Diseases through the Development of Novel Anti-infectives)
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Review

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16 pages, 996 KiB  
Review
Candida auris: A Quick Review on Identification, Current Treatments, and Challenges
by Lucia Černáková, Maryam Roudbary, Susana Brás, Silva Tafaj and Célia F. Rodrigues
Int. J. Mol. Sci. 2021, 22(9), 4470; https://doi.org/10.3390/ijms22094470 - 25 Apr 2021
Cited by 44 | Viewed by 9608
Abstract
Candida auris is a novel and major fungal pathogen that has triggered several outbreaks in the last decade. The few drugs available to treat fungal diseases, the fact that this yeast has a high rate of multidrug resistance and the occurrence of misleading [...] Read more.
Candida auris is a novel and major fungal pathogen that has triggered several outbreaks in the last decade. The few drugs available to treat fungal diseases, the fact that this yeast has a high rate of multidrug resistance and the occurrence of misleading identifications, and the ability of forming biofilms (naturally more resistant to drugs) has made treatments of C. auris infections highly difficult. This review intends to quickly illustrate the main issues in C. auris identification, available treatments and the associated mechanisms of resistance, and the novel and alternative treatment and drugs (natural and synthetic) that have been recently reported. Full article
(This article belongs to the Special Issue Tackling New and Reemerging Infectious Diseases through the Development of Novel Anti-infectives)
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19 pages, 1489 KiB  
Review
A Highlight on the Inhibition of Fungal Carbonic Anhydrases as Drug Targets for the Antifungal Armamentarium
by Claudiu T. Supuran and Clemente Capasso
Int. J. Mol. Sci. 2021, 22(9), 4324; https://doi.org/10.3390/ijms22094324 - 21 Apr 2021
Cited by 26 | Viewed by 2999
Abstract
Carbon dioxide (CO2), a vital molecule of the carbon cycle, is a critical component in living organisms’ metabolism, performing functions that lead to the building of compounds fundamental for the life cycle. In all living organisms, the CO2/bicarbonate (HCO [...] Read more.
Carbon dioxide (CO2), a vital molecule of the carbon cycle, is a critical component in living organisms’ metabolism, performing functions that lead to the building of compounds fundamental for the life cycle. In all living organisms, the CO2/bicarbonate (HCO3−) balancing is governed by a superfamily of enzymes, known as carbonic anhydrases (CAs, EC 4.2.1.1). CAs catalyze the pivotal physiological reaction, consisting of the reversible hydration of the CO2 to HCO3− and protons. Opportunistic and pathogenic fungi can sense the environmental CO2 levels, which influence their virulence or environmental subsistence traits. The fungal CO2-sensing is directly stimulated by HCO3− produced in a CA-dependent manner, which directly activates adenylyl cyclase (AC) involved in the fungal spore formation. The interference with CA activity may impair fungal growth and virulence, making this approach interesting for designing antifungal drugs with a novel mechanism of action: the inhibition of CAs linked to the CO2/HCO3−/pH chemosensing and signaling. This review reports that sulfonamides and their bioisosteres as well as inorganic anions can inhibit in vitro the β- and α-CAs from the fungi, suggesting how CAs may be considered as a novel “pathogen protein” target of many opportunistic, pathogenic fungi. Full article
(This article belongs to the Special Issue Tackling New and Reemerging Infectious Diseases through the Development of Novel Anti-infectives)
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