Functional role of phenylacetic acid from metapleural gland secretions in controlling fungal pathogens in evolutionarily derived leaf-cutting ants

Fungus-farming ant colonies vary four to five orders of magnitude in size. They employ compounds from actinomycete bacteria and exocrine glands as antimicrobial agents. Atta colonies have millions of ants and are particularly relevant for understanding hygienic strategies as they have abandoned their ancestors' prime dependence on antibiotic-based biological control in favour of using metapleural gland (MG) chemical secretions. Atta MGs are unique in synthesizing large quantities of phenylacetic acid (PAA), a known but little investigated antimicrobial agent. We show that particularly the smallest workers greatly reduce germination rates of Escovopsis and Metarhizium spores after actively applying PAA to experimental infection targets in garden fragments and transferring the spores to the ants' infrabuccal cavities. In vitro assays further indicated that Escovopsis strains isolated from evolutionarily derived leaf-cutting ants are less sensitive to PAA than strains from phylogenetically more basal fungus-farming ants, consistent with the dynamics of an evolutionary arms race between virulence and control for Escovopsis , but not Metarhizium. Atta ants form larger colonies with more extreme caste differentiation relative to other attines, in societies characterized by an almost complete absence of reproductive conflicts. We hypothesize that these changes are associated with unique evolutionary innovations in chemical pest management that appear robust against selection pressure for resistance by specialized mycopathogens.

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In Vitro Antimicrobial Activity of the Decontaminant HybenX® Compared to Chlorhexidine and Sodium Hypochlorite against Common Bacterial and Yeast Pathogens

Antibiotics ◽

10.3390/antibiotics8040188 ◽

2019 ◽

Vol 8 (4) ◽

pp. 188 ◽

Cited By ~ 3

Author(s):

Alberto Antonelli ◽

Luca Giovannini ◽

Ilaria Baccani ◽

Valentina Giuliani ◽

Riccardo Pace ◽

...

Keyword(s):

Antimicrobial Activity ◽

Sodium Hypochlorite ◽

Fungal Pathogens ◽

Antimicrobial Agents ◽

Fungal Infections ◽

Yeast Strains ◽

Low Concentrations ◽

Endodontic Infections ◽

Reference Strains

The recent increase in infections mediated by drug-resistant bacterial and fungal pathogens underlines the urgent need for novel antimicrobial compounds. In this study, the antimicrobial activity (inhibitory and cidal) of HybenX®, a novel dessicating agent, in comparison with commonly used sodium hypochlorite and chlorhexidine, against a collection of bacterial and yeast strains representative of the most common human pathogenic species was evaluated. The minimal inhibitory, bactericidal, and fungicidal concentrations (MIC, MBC, and MFC, respectively) of the three different antimicrobial agents were evaluated by broth microdilution assays, followed by subculturing of suitable dilutions. HybenX® was active against 26 reference strains representative of staphylococci, enterococci, Enterobacterales, Gram-negative nonfermenters, and yeasts, although at higher concentrations than sodium hypochlorite and chlorhexidine. HybenX® MICs were 0.39% for bacteria (with MBCs ranging between 0.39% and 0.78%), and 0.1–0.78% for yeasts (with MFCs ranging between 0.78% and 1.6%). HybenX® exhibited potent inhibitory and cidal activity at low concentrations against several bacterial and yeast pathogens. These findings suggest that HybenX® could be of interest for the treatment of parodontal and endodontic infections and also for bacterial and fungal infections of other mucous membranes and skin as an alternative to sodium hypochlorite and chlorhexidine.

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Urinary infection in dogs with chronic kidney disease: aetiology and resistance

Semina Ciências Agrárias ◽

10.5433/1679-0359.2019v40n6supl3p3741 ◽

2019 ◽

Vol 40 (6Supl3) ◽

pp. 3741

Author(s):

Ariane Martins Fernandes ◽

Alessandra Tammy Hayakawa Ito de Sousa ◽

Luciana Auxiliadora Viebrantz da Conceição ◽

Felipe Gomes da Silva ◽

Mayara Aparecida Araújo Cayuela ◽

...

Keyword(s):

Urinary Tract ◽

Bacterial Resistance ◽

Antimicrobial Agents ◽

Urine Culture ◽

Urinary Infection ◽

Clinical Routine ◽

Disease Aetiology ◽

Tract Infections ◽

And Control

Infections of the genitourinary system are among the most frequent in the clinical routine of small animals. Treatment with the most appropriate antimicrobial therapy, according to the uropathogen susceptibility test, can avoid the spread of bacterial resistance to antimicrobials. A clinical study was performed in 32 canines, of both sexes and differing ages, who attended the Veterinary Teaching Hospital. Urine samples underwent culture, with the objective of evaluating urinary tract infection in dogs with renal disease, identifying the associated bacterial pathogens, and verifying their antimicrobial susceptibility in vitro. Urine culture was positive in 10 dogs, mostly males, with no predisposition for breed, and a mean age of 8.28 years. Most of the urinary tract infections (UTIs) were monobacterial, with the most common microorganisms being Pseudomonas sp. and Staphylococcus sp. The antimicrobials imipenem and meropenem had the best overall sensitivity profile, and ampicillin showed the highest resistance. The variation in epidemiological profiles, and susceptibility to uropathogens, reinforces the importance of the veterinarian in the prevention and control of infection, in addition to the need for further research to identify new antimicrobial agents.

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Voriconazole: A New Triazole Antifungal Agent

Annals of Pharmacotherapy ◽

10.1345/aph.1c261 ◽

2003 ◽

Vol 37 (3) ◽

pp. 420-432 ◽

Cited By ~ 68

Author(s):

Margaret M Pearson ◽

P David Rogers ◽

John D Cleary ◽

Stanley W Chapman

Keyword(s):

Amphotericin B ◽

Antifungal Agent ◽

Fungal Pathogens ◽

Antimicrobial Agents ◽

Case Reports ◽

Empirical Therapy ◽

Immunocompromised Patients ◽

In Vitro Susceptibility ◽

Medline Search

OBJECTIVE: To review the pharmacology, in vitro susceptibility, pharmacokinetics, clinical efficacy, and adverse effects of voriconazole, a triazole antifungal agent. DATA SOURCES: A MEDLINE search, restricted to English language, was conducted from 1990 to June 2002. Supplementary sources included program abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy and the Infectious Diseases Society of America from 1996 to 2001 and manufacturer information available through the Food and Drug Administration's Web site. DATA EXTRACTION: All published and unpublished trials and abstracts citing voriconazole were selected. DATA SYNTHESIS: Voriconazole has shown in vitro activity against many yeasts and a variety of mold and dermatophyte isolates. Voriconazole can be administered either orally or parenterally. It exhibits good oral bioavailability, wide tissue distribution including distribution into the central nervous system, and hepatic metabolism. Drug interactions occur through inhibition of the CYP2C9, CYP2C19, and CYP3A4 isoenzymes, resulting in alterations in kinetic parameters of either voriconazole or the interacting agent. Efficacy has been illustrated in open, noncomparative studies of aspergillosis in immunocompromised patients. Human case reports describe successful treatment of rare fungal pathogens. The most commonly reported adverse events include visual disturbances and elevations in liver function tests. CONCLUSIONS: Voriconazole is at least as effective as amphotericin B in the treatment of acute invasive aspergillosis in immunocompromised patients. It has similar efficacy as fluconazole in treatment of esophageal candidiasis. Voriconazole did not achieve statistical non-inferiority to liposomal amphotericin B for empirical therapy in patients with neutropenia and persistent fever, diminishing enthusiasm for use in this indication until additional trials are completed. Based on case reports and in vitro efficacy, voriconazole may prove to be a clinically useful agent in the treatment of other fungal disease.

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Efficacy and Pharmacokinetics of Fosmanogepix (APX001) in the Treatment of Candida Endophthalmitis and Hematogenous Meningoencephalitis in Non-neutropenic Rabbits

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01795-20 ◽

2020 ◽

Author(s):

Ruta Petraitiene ◽

Vidmantas Petraitis ◽

Bo Bo Win Maung ◽

Robert S. Mansbach ◽

Michael R. Hodges ◽

...

Keyword(s):

Aqueous Humor ◽

Fungal Pathogens ◽

Rabbit Model ◽

Control Groups ◽

Highly Active ◽

Fungal Enzyme ◽

Plasma Pharmacokinetics ◽

And Control

Candida endophthalmitis is a serious sight-threatening complication of candidemia that may occur before or during antifungal therapy. Hematogenous Candida meningoencephalitis (HCME) is also a serious manifestation of disseminated candidiasis in premature infants, immunosuppressed children, and immunocompromised adults. We evaluated the antifungal efficacy and pharmacokinetics of the prodrug fosmanogepix (APX001) in a rabbit model of endophthalmitis/HCME. Manogepix (APX001A), the active moiety of prodrug fosmanogepix, inhibits the fungal enzyme Gwt1, and is highly active in vitro and in vivo against Candida spp., Aspergillus spp., and other fungal pathogens. Plasma pharmacokinetics of manogepix after oral administration of fosmanogepix on Day-6 at 25, 50, and 100 mg/kg resulted in plasma Cmax of 3.96±0.41, 4.14±1.1, and 11.5±1.1 μg/ml, respectively, and AUC0-12 of 15.8±3.1, 30.8±5.0, 95.9±14 μg·h/ml, respectively. Manogepix penetrated into the aqueous humor, vitreous, and choroid with liquid to plasma ratios ranging from 0.19 to 0.52, 0.09 to 0.12, and 0.02 to 0.04, respectively. These concentrations correlated with a significant decrease in Candida albicans burden in vitreous (>101-103) and choroid (>101-103) (P≤0.05 and P≤0.001, respectively). Aqueous humor had no detectable C. albicans in treatment and control groups. The tissue/plasma concentration ratios of manogepix in meninges, cerebrum, cerebellum, and spinal cord were approximately 1:1, which correlated with a >102-104 decline of C. albicans in tissue vs control (P≤0.05). Serum and CSF (1→3)-β-D-glucan levels demonstrated significant declines in response to fosmanogepix treatment. These findings provide an experimental foundation for fosmanogepix in treatment of Candida endophthalmitis and HCME and de-risk the clinical trials of candidemia and invasive candidiasis.

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Symbiotic Plant Peptides EliminateCandida albicansBothIn Vitroand in an Epithelial Infection Model and Inhibit the Proliferation of Immortalized Human Cells

BioMed Research International ◽

10.1155/2014/320796 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 17

Author(s):

Lilla Ördögh ◽

Andrea Vörös ◽

István Nagy ◽

Éva Kondorosi ◽

Attila Kereszt

Keyword(s):

Fungal Pathogens ◽

Antimicrobial Agents ◽

Therapeutic Potential ◽

Antibacterial Activities ◽

Multidrug Resistant ◽

Infection Model ◽

Small Nodule ◽

Coculture Model ◽

Epithelial Cell Death

The increasing number of multidrug-resistant microbes now emerging necessitates the identification of novel antimicrobial agents. Plants produce a great variety of antimicrobial peptides including hundreds of small, nodule-specific cysteine-rich NCR peptides that, in the legumeMedicago truncatula, govern the differentiation of endosymbiotic nitrogen fixing bacteria and,in vitro, can display potent antibacterial activities. In this study, the potential candidacidal activity of 19 NCR peptides was investigated. Cationic NCR peptides having an isoelectric point above 9 were efficient in killingCandida albicans, one of the most common fungal pathogens of humans. None of the tested NCR peptides were toxic for immortalized human epithelial cells at concentrations that effectively killed the fungus; however, at higher concentrations, some of them inhibited the division of the cells. Furthermore, the cationic peptides successfully inhibitedC. albicansinduced human epithelial cell death in anin vitrococulture model. These results highlight the therapeutic potential of cationic NCR peptides in the treatment of candidiasis.

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Synthesis and In Vitro Antibacterial Evaluation of Schiff Bases Derived FROM 2-Chloro-3-Quinolinecarboxaldehyde

Avicenna Journal of Medical Biochemistry ◽

10.34172/ajmb.2019.03 ◽

2019 ◽

Vol 7 (1) ◽

pp. 9-15

Author(s):

Hamid Beyzaei ◽

Hadis Hosseini Moghadam ◽

Ghodsieh Bagherzade ◽

Reza Aryan ◽

Mohammadreza Moghaddam-Manesh

Keyword(s):

Schiff Bases ◽

Fungal Pathogens ◽

Pathogenic Bacteria ◽

Structural Changes ◽

Antimicrobial Agents ◽

Antimicrobial Properties ◽

Antibiotic Resistant ◽

Heterocyclic Schiff Bases ◽

Time Kill

Background: Design, identification, and synthesis of new antimicrobial agents along with preventive proceedings are essential to confront antibiotic-resistant pathogenic bacteria. Heterocyclic Schiff bases are biologically important compounds whose antimicrobial potentials have been proven to bacterial and fungal pathogens. Objectives: In this study, some quinoline Schiff bases were synthesized from condensation of 2-chloro3-quinolinecarboxaldehyde and aniline derivatives. Their inhibitory activities were evaluated against 6 gram-positive and 2 gram-negative bacterial pathogens. Methods: Disc diffusion, broth microdilution, and time-kill tests were applied according to the CLSI guidelines to determine IZD, MIC, and MBC values. Results: 2-Chloro-3-quinolinecarboxaldehyde Schiff bases could inhibit the growth of bacteria with IZDs of 7.5-19.8 mm, MICs of 256-2048 μg mL-1, and MBCs of 512 to ≥2048 μg mL-1. Conclusion: Moderate antibacterial effects were observed with heterocyclic Schiff bases. Complexation and structural changes can improve their antimicrobial properties.

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Synthesis and Antimicrobial Activities of Novel Rutin Derivatives Carrying Quinoline Moiety

Revista de Chimie ◽

10.37358/rc.20.6.8206 ◽

2020 ◽

Vol 71 (6) ◽

pp. 401-407

Author(s):

Dan Lupascu ◽

Lenuta Profire ◽

Maria Apotrosoaei ◽

Cristina Tuchilus ◽

Ioana Mirela Vasincu ◽

...

Keyword(s):

Fungal Pathogens ◽

Antimicrobial Agents ◽

Antibacterial Activities ◽

Multidrug Resistant ◽

Antimicrobial Activities ◽

Biological Properties ◽

Research Directions ◽

Good Antibacterial Activity ◽

Vegetal Species

Antimicrobial resistance constitutes a topical subject and it is one of the major threats to public health. According to statistics, the incidence of multidrug-resistant microorganisms, such as bacteria, fungi and protozoa has increased in the last decades and it continues to spread. Therefore, the development of novel antimicrobial agents to combat drug-resistant infections is very important, among other research directions in this field. Quinoline ring is a very interesting structure for researchers because of its diverse biological properties (antimicrobial, anticancer, anticonvulsant, antiinflamatory and cardiovascular). On the other hand several studies showed good antibacterial activity (including anti-Pseudomonas effects) and antifungal properties of rutin or vegetal species with a high flavonoids (especially rutin) concentration. Based on the above considerations, eight novel rutin derivatives carrying 4- and 8-aminoquinoline moiety were designed, synthesized and characterized by FTIR, 1H NMR and elemental analysis. All compounds were evaluated for their in vitro antimicrobial activities against representative Gram-positive, Gram-negative and fungal pathogens. The results indicated that all rutin derivatives exhibited good antibacterial activities, similar to ciprofloxacin.

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Looking for New Antifungal Drugs from Flavonoids: Impact of the Genetic Diversity of Candida albicans on the in-vitro Response

Current Medicinal Chemistry ◽

10.2174/0929867325666171226102700 ◽

2019 ◽

Vol 26 (27) ◽

pp. 5108-5123 ◽

Cited By ~ 4

Author(s):

Maria Rosa Felice ◽

Letterio Giuffrè ◽

Lamya El Aamri ◽

Majida Hafidi ◽

Giuseppe Criseo ◽

...

Keyword(s):

Genetic Diversity ◽

Genetic Variation ◽

Candida Albicans ◽

Fungal Pathogens ◽

Antimicrobial Agents ◽

Biological Activities ◽

Antifungal Drugs ◽

Microbial Pathogens ◽

Beneficial Effects

Background:In an era in which antimicrobial resistance is increasing at an alarming pace, it is very important to find new antimicrobial agents effective against pathogenic microrganisms resistant to traditional treatments. Among the notable breakthroughs in the past years of research in natural-drug discovery, there is the identification and testing of flavonoids, a group of plant-derived substances capable of promoting many beneficial effects on humans. These compounds show different biological activities such as inhibition of neuroinflammation and tumor growth as well as antimicrobial activity against many microbial pathogens.Methods:We undertook a review of protocols and standard strains used in studies reporting the inhibitory effects of flavonoids against Candida albicans by focusing our attention on genetic characterization of the strains examined. Moreover, using the C. albicans MLST-database, we performed a phylogenetic analysis showing the genetic variation occurring in this species.Results:Today, we have enough information to estimate genetic diversity within microbial species and recent data revealed that most of fungal pathogens show complex population structures in which not a single isolate can be designated as representative of the entire taxon. This is especially true for the highly divergent fungal pathogen C. albicans, in which the assumption that one or few “standard strains” can represent the whole species is overly unrealistic and should be laid to rest.Conclusion:The goal of this article is to shed light on the extent of genetic variation in C. albicans and how this phenomenon can largely influence the activity of flavonoids against this species.

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Chitinase Chi 2 Positively Regulates Cucumber Resistance against Fusarium oxysporum f. sp. cucumerinum

Genes ◽

10.3390/genes13010062 ◽

2021 ◽

Vol 13 (1) ◽

pp. 62

Author(s):

Jun Xu ◽

Ningyuan Zhang ◽

Ke Wang ◽

Qianqian Xian ◽

Jingping Dong ◽

...

Keyword(s):

Fusarium Oxysporum ◽

Fungal Pathogens ◽

Gene Activation ◽

Resistance Breeding ◽

Growth And Yield ◽

Virus Induced Gene Silencing ◽

Cucumis Sativus L ◽

Acid Pathway ◽

And Control

Cucumber (Cucumis sativus L.) is an important vegetable crop worldwide, and Fusarium wilt (FW), caused by Fusarium oxysporum f. sp. cucumerinum (Foc), severely restricts cucumber growth and yield. Accumulating lines of evidence indicate that chitinases play important roles in attacking the invading fungal pathogens through catalyzing their cell wall degradation. Here, we identified the chitinase (Chi) genes in cucumber and further screened the FW-responsive genes via a comparative transcriptome analysis and found that six common genes were predominantly expressed in roots but also significantly upregulated after Foc infection. Expression verification further conformed that Chi2 and Chi14 were obviously induced by Foc as well as by hormone treatments, compared with the controls. The purified Chi2 and Chi14 proteins significantly affected the growth of Foc in vitro, compared with the controls. Knockdown of Chi2 in cucumber by virus-induced gene silencing (VIGS) increased susceptibility to FW, compared with the Chi14-silenced and control plants, and silencing of Chi2 drastically impaired gene activation in the jasmonic acid pathway, suggesting that the Chi2 gene might play positive roles in cucumber FW defense and, therefore, can provide a gene resource for developing cucumber-FW-resistance breeding programs.

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Lactosmart: A Novel Therapeutic Molecule for Antimicrobial Defense

Frontiers in Microbiology ◽

10.3389/fmicb.2021.672589 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jiya Singh ◽

Viswanathan Vijayan ◽

Saiema Ahmedi ◽

Pradeep Pant ◽

Nikhat Manzoor ◽

...

Keyword(s):

Binding Site ◽

Fungal Pathogens ◽

Md Simulation ◽

Antimicrobial Agents ◽

Shigella Flexneri ◽

Antimicrobial Protein ◽

Simulation Studies ◽

Antimicrobial Defense ◽

Lps Binding

The problem of antibiotic resistance has prompted researchers around the globe to search for new antimicrobial agents. Antimicrobial proteins and peptides are naturally secreted by almost all the living organisms to fight infections and can be safer alternatives to chemical antibiotics. Lactoferrin (LF) is a known antimicrobial protein present in all body secretions. In this study, LF was digested by trypsin, and the resulting hydrolysates were studied with respect to their antimicrobial properties. Among the hydrolysates, a 21-kDa basic fragment of LF (termed lactosmart) showed promise as a new potent antimicrobial agent. The antimicrobial studies were performed on various microorganisms including Shigella flexneri, Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli as well as fungal pathogens such as Candida albicans, Candida tropicalis, and Candida glabrata. In addition, the lipopolysaccharide (LPS)-binding properties of lactosmart were studied using surface plasmon resonance technique in vitro, along with docking of LPS and molecular dynamics (MD) simulation studies. The results showed that lactosmart had better inhibitory effects against pathogenic microorganisms compared to LF. The results of docking and MD simulation studies further validated the tighter binding of LPS to lactosmart compared to LF. The two LPS-binding sites have been characterized structurally in detail. Through these studies, it has been demonstrated that in native LF, only one LPS-binding site remains exposed due to its location being on the surface of the molecule. However, due to the generation of the lactosmart molecule, the second LPS-binding site gets exposed too. Since LPS is an essential and conserved part of the bacterial cell wall, the pro-inflammatory response in the human body caused by LPS can be targeted using the newly identified lactosmart. These findings highlight the immense potential of lactosmart in comparison to native LF in antimicrobial defense. We propose that lactosmart can be further developed as an antibacterial, antifungal, and antibiofilm agent.

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