Abstract:
:This research analyzed six Aspergillus fumigatus genes encoding putative efflux proteins for their roles as transporters. TheA. fumigatus genes abcA, abcC, abcF, abcG, abcH, and abcI were cloned into plasmids and overexpressed in a Saccharomyces cerevisiae strain in which the highly active endogenous ABC transporter gene PDR5 was deleted. The activity of each transporter was measured by efflux of rhodamine 6G and accumulation of alanine β-naphthylamide. The transporters AbcA, AbcC, and AbcF had the strongest efflux activities of these compounds. All of the strains with plasmid-expressed transporters had more efflux activity than did the PDR5-deleted background strain. We performed broth microdilution drug susceptibility testing and agar spot assays using an array of compounds and antifungal drugs to determine the transporter specificity and drug susceptibility of the strains. The transporters AbcC and AbcF showed the broadest range of substrate specificity, while AbcG and AbcH had the narrowest range of substrates. Strains expressing the AbcA, AbcC, AbcF, or AbcI transporter were more resistant to fluconazole than was the PDR5-deleted background strain. Strains expressing AbcC and AbcF were additionally more resistant to clotrimazole, itraconazole, ketoconazole, and posaconazole than was the background strain. Finally, we analyzed the expression levels of the genes by reverse transcription-quantitative PCR (RT-qPCR) in triazole-susceptible and -resistant A. fumigatus clinical isolates. All of these transporters are expressed at a measurable level, and transporter expression varied significantly between strains, demonstrating the high degree of phenotypic variation, plasticity, and divergence of which this species is capable.IMPORTANCE One mechanism behind drug resistance is altered export out of the cell. This work is a multifaceted analysis of membrane efflux transporters in the human fungal pathogen A. fumigatus Bioinformatics evidence infers that there is a relatively large number of genes in A. fumigatus that encode ABC efflux transporters. However, very few of these transporters have been directly characterized and analyzed for their potential role in drug resistance.Our objective was to determine if these undercharacterized proteins function as efflux transporters and then to better define whether their efflux substrates include antifungal drugs used to treat fungal infections. We chose six A. fumigatus potential plasma membrane ABC transporter genes for analysis and found that all six genes produced functional transporter proteins. We used two fungal systems to look for correlations between transporter function and drug resistance. These transporters have the potential to produce drug-resistant phenotypes in A. fumigatus Continued characterization of these and other transporters may assist in the development of efflux inhibitor drugs.
journal_name
mBiojournal_title
mBioauthors
Esquivel BD,Rybak JM,Barker KS,Fortwendel JR,Rogers PD,White TCdoi
10.1128/mBio.00338-20subject
Has Abstractpub_date
2020-03-24 00:00:00issue
2issn
2150-7511pii
mBio.00338-20journal_volume
11pub_type
杂志文章相关文献
mBio文献大全abstract::Throughout history, the yeast Saccharomyces cerevisiae has played a central role in human society due to its use in food production and more recently as a major industrial and model microorganism, because of the many genetic and genomic tools available to probe its biology. However, S. cerevisiae has proven difficult ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01410-18
更新日期:2018-09-25 00:00:00
abstract:UNLABELLED:The newly emerging Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe respiratory infection with a high mortality rate (~35%). MERS-CoV has been a global threat due to continuous outbreaks in the Arabian peninsula and international spread by infected travelers since 2012. From May to Jul...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00019-16
更新日期:2016-03-01 00:00:00
abstract:UNLABELLED:Clostridium perfringens enterotoxin (CPE) contributes to several important human gastrointestinal (GI) diseases. This toxin and its derivatives are also being explored for translational applications, i.e., cancer therapy or drug delivery. Some, but not all, members of the 24-member claudin (Cldn) family of m...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00594-12
更新日期:2013-01-15 00:00:00
abstract:UNLABELLED:Sensing of and responding to environmental changes are of vital importance for microbial cells. Consequently, bacteria have evolved a plethora of signaling systems that usually sense biochemical cues either via direct ligand binding, thereby acting as "concentration sensors," or by responding to downstream e...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00975-15
更新日期:2015-07-21 00:00:00
abstract::Long noncoding RNA (lncRNA) plays important roles in sexual development in eukaryotes. In filamentous fungi, however, little is known about the expression and roles of lncRNAs during fruiting body formation. By profiling developmental transcriptomes during the life cycle of the plant-pathogenic fungus Fusarium gramine...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01292-18
更新日期:2018-08-14 00:00:00
abstract:UNLABELLED:Mammalian lipopolysaccharide (LPS) binding proteins (LBPs) occur mainly in extracellular fluids and promote LPS delivery to specific host cell receptors. The function of LBPs has been studied principally in the context of host defense; the possible role of LBPs in nonpathogenic host-microbe interactions has ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01193-15
更新日期:2015-10-13 00:00:00
abstract:UNLABELLED:West Nile virus (WNV) is an emerging neuroinvasive flavivirus that now causes significant morbidity and mortality worldwide. The innate and adaptive immune responses to WNV infection have been well studied in C57BL/6J inbred mice, but this model lacks the variations in susceptibility, immunity, and outcome t...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00493-15
更新日期:2015-05-05 00:00:00
abstract::Enterohemorrhagic Escherichia coli (EHEC) is a major cause of foodborne gastrointestinal illness. EHEC uses a specialized type III secretion system (T3SS) to form attaching and effacing lesions in the colonic epithelium and outcompete commensal gut microbiota to cause disease. A recent report in mBio (E. A. Cameron, M...
journal_title:mBio
pub_type: 评论,杂志文章
doi:10.1128/mBio.00115-19
更新日期:2019-02-26 00:00:00
abstract::Streptococcus gallolyticus subsp. gallolyticus is an emerging opportunistic pathogen responsible for septicemia and endocarditis in the elderly. Invasive infections by S. gallolyticus subsp. gallolyticus are strongly linked to the occurrence of colorectal cancer (CRC). It was previously shown that increased secondary ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.03189-20
更新日期:2021-01-05 00:00:00
abstract::Protein kinase R (PKR) plays a major role in activating host immunity during infection by sensing double-stranded RNA (dsRNA) produced by viruses. Once activated by dsRNA, PKR phosphorylates the translation factor eukaryotic initiation factor 2α (eIF2α), halting cellular translation. Many viruses have methods of inhib...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00668-19
更新日期:2019-04-23 00:00:00
abstract::Staphylococcus aureus is an important human pathogen whose success is largely attributed to its vast arsenal of virulence factors that facilitate its invasion into, and survival within, the human host. The expression of these virulence factors is controlled by the quorum sensing accessory gene regulator (Agr) system. ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00796-19
更新日期:2019-08-06 00:00:00
abstract::Pneumocystis species are opportunistic mammalian pathogens that cause severe pneumonia in immunocompromised individuals. These fungi are highly host specific and uncultivable in vitro Human Pneumocystis infections present major challenges because of a limited therapeutic arsenal and the rise of drug resistance. To inv...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00381-18
更新日期:2018-05-08 00:00:00
abstract::Reactive oxygen species (ROS) are produced by host phagocytes and exert antimicrobial actions against a broad range of pathogens. The observable antimicrobial actions of ROS are highly dependent on experimental conditions. This perspective reviews recent controversies regarding ROS in Salmonella-phagocyte interactions...
journal_title:mBio
pub_type: 杂志文章,评审
doi:10.1128/mBio.00141-11
更新日期:2011-09-06 00:00:00
abstract:UNLABELLED:Human immunodeficiency virus type 1 (HIV-1) Nef enhances virus replication and contributes to immune evasion in vivo, but the underlying molecular mechanisms remain incompletely defined. Nef interferes with host cell actin dynamics to restrict T lymphocyte responses to chemokine stimulation and T cell recept...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01309-15
更新日期:2015-09-08 00:00:00
abstract::Can accumulation of a normally transient metabolite affect fungal biology? UDP-4-keto-6-deoxyglucose (UDP-KDG) represents an intermediate stage in conversion of UDP-glucose to UDP-rhamnose. Normally, UDP-KDG is not detected in living cells, because it is quickly converted to UDP-rhamnose by the enzyme UDP-4-keto-6-deo...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01559-17
更新日期:2017-11-21 00:00:00
abstract:UNLABELLED:Curing HIV-1 infection will require elimination of persistent cellular reservoirs that harbor latent virus in the face of combination antiretroviral therapy (cART). Proposed immunotherapeutic strategies to cure HIV-1 infection include enhancing lysis of these infected cells by cytotoxic T lymphocytes (CTL). ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00473-16
更新日期:2016-05-31 00:00:00
abstract::Pseudomonas aeruginosa produces an extracellular biofilm matrix that consists of nucleic acids, exopolysaccharides, lipid vesicles, and proteins. In general, the protein component of the biofilm matrix is poorly defined and understudied relative to the other major matrix constituents. While matrix proteins have been s...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00543-18
更新日期:2018-04-10 00:00:00
abstract::Bacteria of the phylum Bacteroidetes, including commensal organisms and opportunistic pathogens, harbor abundant surface-exposed multiprotein membrane complexes (Sus-like systems) involved in carbohydrate acquisition. These complexes have been mostly linked to commensalism, and in some instances, they have also been s...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01232-16
更新日期:2016-10-25 00:00:00
abstract::Streptococcus pneumoniae, a major cause of pneumonia, sepsis, and meningitis worldwide, has the nasopharynges of small children as its main ecological niche. Depletion of pneumococci from this niche would reduce the disease burden and could be achieved using small molecules with narrow-spectrum antibacterial activity....
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.03027-20
更新日期:2020-12-15 00:00:00
abstract:UNLABELLED:The acquisition, delivery, and incorporation of metals into their respective metalloproteins are important cellular processes. These processes are tightly controlled in order to prevent exposure of cells to free-metal concentrations that could yield oxidative damage. Copper (Cu) is one such metal that is req...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00293-11
更新日期:2012-01-31 00:00:00
abstract::The ability to withstand UV damage shapes the ecology of microbes. While mechanisms of UV tolerance were extensively investigated in microorganisms regularly exposed to the sun, far less is known about UV repair of soilborne microorganisms. Fusarium oxysporum is a soilborne fungal plant pathogen that is resistant to U...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02623-19
更新日期:2019-12-03 00:00:00
abstract::Stenotrophomonas maltophilia is a Gram-negative, nonfermenting, environmental bacillus that is an important cause of nosocomial infections, primarily associated with the respiratory tract in the immunocompromised population. Aiming to understand the population structure, microbiological characteristics and impact of a...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00405-19
更新日期:2019-07-02 00:00:00
abstract::During DNA replication, stalling can occur when the replicative DNA polymerases encounter lesions or hard-to replicate regions. Under these circumstances, the processivity factor PCNA gets ubiquitylated at lysine 164, inducing the DNA damage tolerance (DDT) mechanisms that can bypass lesions encountered during DNA rep...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00705-20
更新日期:2020-05-05 00:00:00
abstract:UNLABELLED:Human cathepsin W (CtsW) is a cysteine protease, which was identified in a genome-wide RNA interference (RNAi) screen to be required for influenza A virus (IAV) replication. In this study, we show that reducing the levels of expression of CtsW reduces viral titers for different subtypes of IAV, and we map th...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00297-15
更新日期:2015-06-09 00:00:00
abstract:UNLABELLED:Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of human Kaposi's sarcoma, a tumor that arises from endothelial cells, as well as two B cell lymphoproliferative diseases, primary effusion lymphoma and multicentric Castleman's disease. KSHV utilizes a variety of mechanisms to evade host ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01499-15
更新日期:2015-12-08 00:00:00
abstract:UNLABELLED:Large-scale rearrangements may be important in evolution because they can alter chromosome organization and gene expression in ways not possible through point mutations. In a long-term evolution experiment, twelve Escherichia coli populations have been propagated in a glucose-limited environment for over 25 ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01377-14
更新日期:2014-09-09 00:00:00
abstract::Trauma-related necrotizing myocutaneous mucormycosis (NMM) has a high morbidity and mortality in victims of combat-related injuries, geometeorological disasters, and severe burns. Inspired by the observation that several recent clusters of NMM have been associated with extreme mechanical forces (e.g., during tornados)...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01414-20
更新日期:2020-06-30 00:00:00
abstract::Lassa virus (LASV) infection is a major public health concern due to high fatality rates and limited effective treatment. The interferon-stimulated gene cholesterol 25-hydroxylase (CH25H) encodes an enzyme that catalyzes the production of 25-hydroxycholesterol (25HC). 25HC is involved in regulating cholesterol biosynt...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01808-16
更新日期:2016-12-20 00:00:00
abstract:UNLABELLED:Helicobacter pylori chronically infects the gastric mucosa in more than half of the human population; in a subset of this population, its presence is associated with development of severe disease, such as gastric cancer. Genomic analysis of several strains has revealed an extensive H. pylori pan-genome, like...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00239-11
更新日期:2011-11-15 00:00:00
abstract::Estrogen, a major female sex steroid hormone, has been shown to promote the selection of mucoid Pseudomonas aeruginosa in the airways of patients with chronic respiratory diseases, including cystic fibrosis. This results in long-term persistence, poorer clinical outcomes, and limited therapeutic options. In this study...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01774-20
更新日期:2020-09-29 00:00:00