The skin’s epidermis is an essential barrier as the first guard against invading pathogens, and physical protector from external
injury. The skin microbiome, which consists of numerous bacteria, fungi, viruses, and archaea on the epidermis, play a key
role in skin homeostasis. Antibiotics are a fast-acting and effective treatment method, however, antibiotic use is a nuisance
that can disrupt skin homeostasis by eradicating beneficial bacteria along with the intended pathogens and cause antibioticresistant
bacteria spread. Increased numbers of antimicrobial peptides (AMPs) derived from humans and bacteria have been
reported, and their roles have been well defined. Recently, modulation of the skin microbiome with AMPs rather than artificially
synthesized antibiotics has attracted the attention of researchers as many antibiotic-resistant strains make treatment
mediation difficult in the context of ecological problems. Herein, we discuss the overall insights into the skin microbiome,
including its regulation by different AMPs, as well as their composition and role in health and disease.
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Plants rooted in soil have intimate associations with a diverse
array of soil microorganisms. While the microbial diversity
of soil is enormous, the predominant bacterial phyla
associated with plants include Actinobacteria, Bacteroidetes,
Firmicutes, Proteobacteria, and Verrucomicrobia. Plants supply
nutrient niches for microbes, and microbes support plant
functions such as plant growth, development, and stress tolerance.
The interdependent interaction between the host plant
and its microbes sculpts the plant microbiota. Plant and microbiome
interactions are a good model system for understanding
the traits in eukaryotic organisms from a holobiont
perspective. The holobiont concept of plants, as a consequence
of co-evolution of plant host and microbiota, treats
plants as a discrete ecological unit assembled with their microbiota.
Dissection of plant-microbiome interactions is highly
complicated; however, some reductionist approaches are useful,
such as the synthetic community method in a gnotobiotic
system. Deciphering the interactions between plant and microbiome
by this reductionist approach could lead to better
elucidation of the functions of microbiota in plants. In addition,
analysis of microbial communities’ interactions would
further enhance our understanding of coordinated plant microbiota
functions. Ultimately, better understanding of plantmicrobiome
interactions could be translated to improvements
in plant productivity.
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5-Fluorouracil (5-FU) is an essential drug in systemic chemotherapy
treatments for colorectal cancer (CRC). Despite
the development of several treatment strategies over the past
decades, the patient benefits of 5-FU-based therapies have
been compromised by the development of chemoresistance.
Differences in treatment responses among CRC patients may
be due to genetic and epigenetic factors unique to individuals.
Therefore, important factors for realizing personalized medicine
are to accurately understand the causes and mechanisms
of drug resistance to 5-FU-based therapies and to identify
and validate prognostic biomarkers. Gut microbes that
interact directly with the host contribute to human health
and cancer control. Lactobacillus plantarum, in particular, has
the potential to be a therapeutic agent by producing bioactive
compounds that may benefit the host. Here, we investigated
the gamma-aminobutyric acid (GABA) and GABAB
receptor (GABABR)-dependent signaling pathway as a treatment
option for 5-FU-resistant HT-29 cells. GABA-producing
L. plantarum activates anti-proliferative, anti-migration,
and anti-invasion effects against 5-FU-resistant HT-29 cells.
The inhibitory effects of GABA-producing L. plantarum are
mediated via GABABR. Activated GABABR induces apoptosis
through the inhibition of cAMP-dependent signaling
pathways and cellular inhibitor of apoptosis protein 2 (cIAP2)
expression. Thus, the GABAergic system has potential in 5-
FU-resistant HT-29 cells as a predictive biomarker. In addition,
GABA-producing L. plantarum is promising as an adjuvant
treatment for 5-FU-resistant CRC, and its intervention
in neurobiological signaling imply new possibilities for
chemoprevention and the treatment of colon cancer-related
diseases.
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We employed a stepwise selection model for investigating the
dynamics of antibiotic-resistant variants in Escherichia coli
K-12 treated with increasing concentrations of ciprofloxacin
(CIP). Firstly, we used Sanger sequencing to screen the variations
in the fluoquinolone target genes, then, employed Illumina
NGS sequencing for amplicons targeted regions with
variations. The results demonstrated that variations G81C in
gyrA and K276N and K277L in parC are standing resistance
variations (SRVs), while S83A and S83L in gyrA and G78C
in parC were emerging resistance variations (ERVs). The variants
containing SRVs and/or ERVs were selected successively
based on their sensitivities to CIP. Variant strain 1, containing
substitution G81C in gyrA, was immediately selected
following ciprofloxacin exposure, with obvious increases in
the parC SRV, and parC and gyrA ERV allele frequencies.
Variant strain 2, containing the SRVs, then dominated the
population following a 20× increase in ciprofloxacin concentration,
with other associated allele frequencies also elevated.
Variant strains 3 and 4, containing ERVs in gyrA and parC,
respectively, were then selected at 40× and 160× antibiotic
concentrations. Two variants, strains 5 and 6, generated in
the selection procedure, were lost because of higher fitness
costs or a lower level of resistance compared with variants 3
and 4. For the second induction, all variations/indels were
already present as SRVs and selected out step by step at different
passages. Whatever the first induction or second induction,
our results confirmed the soft selective sweep hypothesis
and provided critical information for guiding clinical
treatment of pathogens containing SRVs.
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Could traces of fluoroquinolones in food induce ciprofloxacin resistance in
Escherichia coli
and
Klebsiella pneumoniae
? An
in vivo
study in
Galleria mellonel Zina Gestels, Yuliia Baranchyk, Dorien Van den Bossche, Jolein Laumen, Said Abdellati, Basil Britto Xavier, Sheeba Santhini Manoharan-Basil, Chris Kenyon, Sadjia Bekal, Mustafa Sadek Microbiology Spectrum.2024;[Epub] CrossRef
The yeast Candida albicans is a member of the microbiota
in the gastrointestinal and urogenital tracts of most healthy
persons, but it can also cause symptomatic infections, especially
in immunocompromised patients. During the life-long
association with its human host, C. albicans generates genetically
altered variants that are better adapted to changes in
their environment. A prime example of this microevolution
is the development of resistance to the commonly used drug
fluconazole, which inhibits ergosterol biosynthesis, during
antimycotic therapy. Fluconazole resistance can be caused by
mutations in the drug target, by changes in the sterol biosynthesis
pathway, and by gain-of-function mutations in transcription
factors that result in the constitutive upregulation
of ergosterol biosynthesis genes and multidrug efflux pumps.
Fluconazole also induces genomic rearrangements that result
in gene amplification and loss of heterozygosity for resistance
mutations, which further increases drug resistance.
These genome alterations may affect extended chromosomal
regions and have additional phenotypic consequences. A
striking case is the loss of heterozygosity for the mating type
locus MTL in many fluconazole-resistant clinical isolates,
which allows the cells to switch to the mating-competent opaque
phenotype. This, in turn, raises the possibility that sexual
recombination between different variants of an originally clonal,
drug-susceptible population may contribute to the generation
of highly fluconazole-resistant strains with multiple
resistance mechanisms. The gain-of-function mutations in
transcription factors, which result in deregulated gene expression,
also cause reduced fitness. In spite of this, many clinical
isolates that contain such mutations do not exhibit fitness defects,
indicating that they have overcome the costs of drug
resistance with further evolution by still unknown mechanisms.
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Two different types of tandem sequences mediate the overexpression of
TinCYP51B
in azole-resistant
Trichophyton indotineae
Tsuyoshi Yamada, Mari Maeda, Hiroaki Nagai, Karine Salamin, Yun-Tsan Chang, Emmanuella Guenova, Marc Feuermann, Michel Monod, Andreas H. Groll Antimicrobial Agents and Chemotherapy.2023;[Epub] CrossRef
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Synergistic Effect of the Combination of Deferoxamine and Fluconazole
In Vitro
and
In Vivo
against Fluconazole-Resistant
Candida
Spp.
Lulu An, Jingwen Tan, Yuanyuan Wang, Siyu Liu, Yongyong Li, Lianjuan Yang Antimicrobial Agents and Chemotherapy.2022;[Epub] CrossRef
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Journal of Medical Microbiology
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Hinokitiol chelates intracellular iron to retard fungal growth by disturbing mitochondrial respiration Xueyang Jin, Ming Zhang, Jinghui Lu, Ximeng Duan, Jinyao Chen, Yue Liu, Wenqiang Chang, Hongxiang Lou Journal of Advanced Research.2021; 34: 65. CrossRef
Lysinibacillus Isolate MK212927: A Natural Producer of Allylamine Antifungal ‘Terbinafine’ Sayed E. El-Sayed, Neveen A. Abdelaziz, Hosam-Eldin Hussein Osman, Ghadir S. El-Housseiny, Ahmed E. Aleissawy, Khaled M. Aboshanab Molecules.2021; 27(1): 201. CrossRef
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The phosphatome of opportunistic pathogen Candida species Krisztina Szabó, Márton Miskei, Ilona Farkas, Viktor Dombrádi Fungal Biology Reviews.2021; 35: 40. CrossRef
Azole-triphenylphosphonium conjugates combat antifungal resistance and alleviate the development of drug-resistance Xin Wang, Jun Liu, Jinyao Chen, Ming Zhang, Chuan Tian, Xiaoping Peng, Gang Li, Wenqiang Chang, Hongxiang Lou Bioorganic Chemistry.2021; 110: 104771. CrossRef
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Identification and Characterization of Mediators of Fluconazole Tolerance in Candida albicans Eric Delarze, Ludivine Brandt, Emilie Trachsel, Marion Patxot, Claire Pralong, Fabio Maranzano, Murielle Chauvel, Mélanie Legrand, Sadri Znaidi, Marie-Elisabeth Bougnoux, Christophe d’Enfert, Dominique Sanglard Frontiers in Microbiology.2020;[Epub] CrossRef
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Dispiropyrrolidine tethered piperidone heterocyclic hybrids with broad-spectrum antifungal activity against Candida albicans and Cryptococcus neoformans Sarah Lawson, Natarajan Arumugam, Abdulrahman I. Almansour, Raju Suresh Kumar, Shankar Thangamani Bioorganic Chemistry.2020; 100: 103865. CrossRef
Lipid composition and cell surface hydrophobicity of Candida albicans influence the efficacy of fluconazole–gentamicin treatment Jakub Suchodolski, Jakub Muraszko, Aleksandra Korba, Przemysław Bernat, Anna Krasowska Yeast.2020; 37(1): 117. CrossRef
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Genotype, biofilm formation ability and specific gene transcripts characteristics of endodontic Enterococcus faecalis under glucose deprivation condition Yawen Liu, Yifan Ping, Yuhua Xiong, Ruyu Zhou, Fulu Xu, Juan Wang, Jin Li Archives of Oral Biology.2020; 118: 104877. CrossRef
Improved Methods of Extraction and In Vitro Evaluation of Antimicrobial Potential of Stem Bark of Terminalia arjuna Sarita Khatkar, Arun Nanda, Shahid Husain Ansari Current Biochemical Engineering.2019; 5(1): 50. CrossRef
The small GTPase Rhb1 is involved in the cell response to fluconazole inCandida albicans Yu-Wen Chen, Ying-Chieh Yeh, Hsueh-Fen Chen, Ruei-Ching Chen, Guan-Yu Lin, Yu-Ting Chen, Chung-Yu Lan FEMS Yeast Research.2019;[Epub] CrossRef
The Magnitude ofCandida albicansStress-Induced Genome Instability Results from an Interaction Between Ploidy and Antifungal Drugs Ognenka Avramovska, Meleah A Hickman G3 Genes|Genomes|Genetics.2019; 9(12): 4019. CrossRef
Cytochalasans from the Endophytic Fungus Xylaria cf. curta with Resistance Reversal Activity against Fluconazole-Resistant Candida albicans Wen-Xuan Wang, Xinxiang Lei, Hong-Lian Ai, Xue Bai, Jing Li, Juan He, Zheng-Hui Li, Yong-Sheng Zheng, Tao Feng, Ji-Kai Liu Organic Letters.2019; 21(4): 1108. CrossRef
Antifungal Activity of a Hydroethanolic Extract From Astronium urundeuva Leaves Against Candida albicans and Candida glabrata Bruna Vidal Bonifácio, Taissa Vieira Machado Vila, Isadora Fantacini Masiero, Patrícia Bento da Silva, Isabel Cristiane da Silva, Érica de Oliveira Lopes, Matheus Aparecido dos Santos Ramos, Leonardo Perez de Souza, Wagner Vilegas, Fernando Rogério Pavan, Frontiers in Microbiology.2019;[Epub] CrossRef
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The Impact of Gene Dosage and Heterozygosity on the Diploid Pathobiont Candida albicans Shen-Huan Liang, Richard J. Bennett Journal of Fungi.2019; 6(1): 10. CrossRef
Evolution of Fluconazole-Resistant Candida albicans Strains by Drug-Induced Mating Competence and Parasexual Recombination Christina Popp, Bernardo Ramírez-Zavala, Sonja Schwanfelder, Ines Krüger, Joachim Morschhäuser, Judith Berman mBio.2019;[Epub] CrossRef
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Elevation of cell wall chitin via Ca2+–calcineurin‐mediated PKC signaling pathway maintains the viability of Candida albicans in the absence of β‐1,6‐glucan synthesis Qi Han, Na Wang, Chaoying Pan, Yue Wang, Jianli Sang Molecular Microbiology.2019; 112(3): 960. CrossRef
Azole Resistance Reduces Susceptibility to the Tetrazole Antifungal VT-1161 Brian C. Monk, Mikhail V. Keniya, Manya Sabherwal, Rajni K. Wilson, Danyon O. Graham, Harith F. Hassan, Danni Chen, Joel D. A. Tyndall Antimicrobial Agents and Chemotherapy.2019;[Epub] CrossRef
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Two New 1,3,4-Oxadiazoles With Effective Antifungal Activity Against Candida albicans Isis Regina Grenier Capoci, Karina Mayumi Sakita, Daniella Renata Faria, Franciele Abigail Vilugron Rodrigues-Vendramini, Glaucia Sayuri Arita, Admilton Gonçalves de Oliveira, Maria Sueli Felipe, Bernard Maigret, Patricia de Souza Bonfim-Mendonça, Erika S Frontiers in Microbiology.2019;[Epub] CrossRef
Anti-candidal activity of selected analgesic drugs used alone and in combination with fluconazole, itraconazole, voriconazole, posaconazole and isavuconazole J. Król, U. Nawrot, M. Bartoszewicz Journal de Mycologie Médicale.2018; 28(2): 327. CrossRef
Blad-containing oligomer: a novel fungicide used in crop protection as an alternative treatment for tinea pedis and tinea versicolor Alexandra Carreira, João Boavida Ferreira, Iliana Pereira, João Ferreira, Paulo Filipe, Ricardo Boavida Ferreira, Sara Monteiro Journal of Medical Microbiology.2018; 67(2): 198. CrossRef
Varying susceptibility of clinical and environmental Scedosporium isolates to chemical oxidative stress in conidial germination Cindy Staerck, Charlotte Godon, Jean-Philippe Bouchara, Maxime J. J. Fleury Archives of Microbiology.2018; 200(3): 517. CrossRef
Rice Defensin OsAFP1 is a New Drug Candidate against Human Pathogenic Fungi Akihito Ochiai, Kodai Ogawa, Minami Fukuda, Masahiro Ohori, Takumi Kanaoka, Takaaki Tanaka, Masayuki Taniguchi, Yoshiyuki Sagehashi Scientific Reports.2018;[Epub] CrossRef
Thiobarbiturates as potential antifungal agents to control human infections caused by Candida and Cryptococcus species Muhammad Shabeer, Luiz C. A. Barbosa, Milandip Karak, Amanda C. S. Coelho, Jacqueline A. Takahashi Medicinal Chemistry Research.2018; 27(4): 1043. CrossRef
A Case for Antifungal Stewardship Rachel A. Miller Current Fungal Infection Reports.2018; 12(1): 33. CrossRef
A Hyperactive Form of the Zinc Cluster Transcription Factor Stb5 Causes
YOR1
Overexpression and Beauvericin Resistance in Candida albicans
Bernardo Ramírez-Zavala, Hannah Manz, Frank Englert, P. David Rogers, Joachim Morschhäuser Antimicrobial Agents and Chemotherapy.2018;[Epub] CrossRef
Current treatment options for vulvovaginal candidiasis caused by azole-resistant Candida species J. D. Sobel, R. Sobel Expert Opinion on Pharmacotherapy.2018; 19(9): 971. CrossRef
CYP51 as drug targets for fungi and protozoan parasites: past, present and future Galina I. Lepesheva, Laura Friggeri, Michael R. Waterman Parasitology.2018; 145(14): 1820. CrossRef
TLS dependent and independent functions of DNA polymerase eta (Polη/Rad30) from Pathogenic Yeast Candida albicans Kodavati Manohar, Doureradjou Peroumal, Narottam Acharya Molecular Microbiology.2018; 110(5): 707. CrossRef
Potential effect of 2-isopropyl-5-methylphenol (thymol) alone and in combination with fluconazole against clinical isolates of Candida albicans, C. glabrata and C. krusei A. Sharifzadeh, A.R. Khosravi, H. Shokri, H. Shirzadi Journal de Mycologie Médicale.2018; 28(2): 294. CrossRef
Fluconazole-Pyridoxine Bis-Triazolium Compounds with Potent Activity against Pathogenic Bacteria and Fungi Including Their Biofilm-Embedded Forms Marsel R. Garipov, Roman S. Pavelyev, Svetlana A. Lisovskaya, Elena V. Nikitina, Airat R. Kayumov, Alina E. Sabirova, Oksana V. Bondar, Albina G. Malanyeva, Alexander M. Aimaletdinov, Alfia G. Iksanova, Konstantin V. Balakin, Yurii G. Shtyrlin Journal of Chemistry.2017; 2017: 1. CrossRef
Bridging the Gap to Non-toxic Fungal Control: Lupinus-Derived Blad-Containing Oligomer as a Novel Candidate to Combat Human Pathogenic Fungi Ana M. Pinheiro, Alexandra Carreira, Thomas A. K. Prescott, Ricardo B. Ferreira, Sara A. Monteiro Frontiers in Microbiology.2017;[Epub] CrossRef
An acquired mechanism of antifungal drug resistance simultaneously enables Candida albicans to escape from intrinsic host defenses Irene A. I. Hampe, Justin Friedman, Mira Edgerton, Joachim Morschhäuser, Julia Ruth Koehler PLOS Pathogens.2017; 13(9): e1006655. CrossRef
Antimicrobial activity of
Buchenavia tetraphylla
against
Candida albicans
strains isolated from vaginal secretions
José Robson Neves Cavalcanti Filho, Tiago Fonseca Silva, Woah Queiroz Nobre, Larissa Isabela Oliveira de Souza, Cristiane Santos Silva e Silva Figueiredo, Regina Celia Bressan Queiroz de Figueiredo, Norma Buarque de Gusmão, Márcia Vanusa Silva, Luís Cláud Pharmaceutical Biology.2017; 55(1): 1521. CrossRef
Antifungal Resistance: An Emerging Reality and A Global Challenge Dimitrios P Kontoyiannis The Journal of Infectious Diseases.2017; 216(suppl_3): S431. CrossRef
Candida albicans Swi/Snf and Mediator Complexes Differentially Regulate Mrr1-Induced
MDR1
Expression and Fluconazole Resistance
Zhongle Liu, Lawrence C. Myers Antimicrobial Agents and Chemotherapy.2017;[Epub] CrossRef
Structural analyses of Candida albicans sterol 14α-demethylase complexed with azole drugs address the molecular basis of azole-mediated inhibition of fungal sterol biosynthesis Tatiana Y. Hargrove, Laura Friggeri, Zdzislaw Wawrzak, Aidong Qi, William J. Hoekstra, Robert J. Schotzinger, John D. York, F. Peter Guengerich, Galina I. Lepesheva Journal of Biological Chemistry.2017; 292(16): 6728. CrossRef
The natural compound magnolol affects growth, biofilm formation, and ultrastructure of oral Candida isolates Jawad Behbehani, Sheikh Shreaz, Mohammad Irshad, Maribassapa Karched Microbial Pathogenesis.2017; 113: 209. CrossRef
The Structure of Thymidylate Kinase from Candida albicans Reveals a Unique Structural Element Kaustubh Sinha, Gordon S. Rule Biochemistry.2017; 56(33): 4360. CrossRef
Histone Acetyltransferase Encoded by
NGG1
is Required for Morphological Conversion and Virulence of
Candida Albicans
De-Dong Li, Beth Burgwyn Fuchs, Yan Wang, Xiao-Wen Huang, Dan-Dan Hu, Yan Sun, Dong Chai, Yuan-Ying Jiang, Eleftherios Mylonakis Future Microbiology.2017; 12(16): 1497. CrossRef
Human fungal pathogens: Why should we learn? Jeong-Yoon Kim Journal of Microbiology.2016; 54(3): 145. CrossRef
Candidaspecies isolated from different body sites and their antifungal susceptibility pattern: Cross-analysis ofCandida albicansandCandida glabratabiofilms Valentina Cataldi, Emanuela Di Campli, Paolo Fazii, Tonino Traini, Luigina Cellini, Mara Di Giulio Medical Mycology.2016; : myw126. CrossRef
The effects of various 2, 4-D-degradative plasmids on the axenic growth patterns, the degradation phenotypes, and the competitiveness of different host bacteria were evaluated in liquid cultures; the organisms and plasmids used were Alcaligenes eutrophus JMP134/pJP4, Alcaligenes paradoxus/p2811, Pseudomonas pickettii/p712, pJP4, and p712 or p 2811 exhibited very different restriction fragment profiles in restriction endonuclease digests. These plasmids were transferred to the recipients (P. cepacia and Alcaligenes JMP228) at relatively high frequencies ranging from 8.9 × 10^-3 to 1.6 × 10^-5 per donor cell. In the axenic liquid cultures the fast-growing strains, such as P. pseudomallei/p745 and P. cepacia/pJP4, exhibited short lag periods, high specific growth rates, and high relative fitness coefficients, while the slow-growing strains, such as P. pickettii/p712 and A. paradoxus/p2811, had long lag periods, low specific growth rates, and low relative fitness coefficients. Depending on the type of plasmid containing the genes for the 2, 4-D pathway, some transconjugants exhibited intermediate growth patterns between the fast-growing strains and the slow-growing strains. The plasmid and plasmid-host interactions determined specific growth rate and lag time, respectively, which were shown to be principal determinants of competitiveness among the strains, but relative fitness coefficient derived from the axenic culture was not always predictive for the mixed culture condition.