Richard Cannon is Professor of Molecular Microbiology at the University of Otago Faculty of Dentistry. He received his PhD from the University of Cambridge for the study of yeast/mycelial dimorphism in the human fungal pathogen Candida albicans. He has continued this research at the University of Otago focusing on how yeast adhere to oral surfaces, antifungal drug discovery, and mechanisms of fungal drug resistance. His laboratory has developed a system for the heterologous expression of membrane proteins in the model yeast Saccharomyces cerevisiae, and they have used this system to study the structure and function of fungal ATP-binding cassette efflux pumps.
In the last decade, immune checkpoint blockade (ICB) has revolutionized the standard of treatment... more In the last decade, immune checkpoint blockade (ICB) has revolutionized the standard of treatment for solid tumors. Despite success in several immunogenic tumor types evidenced by improved survival, ICB remains largely unresponsive, especially in “cold tumors” with poor lymphocyte infiltration. In addition, side effects such as immune-related adverse events (irAEs) are also obstacles for the clinical translation of ICB. Recent studies have shown that focused ultrasound (FUS), a non-invasive technology proven to be effective and safe for tumor treatment in clinical settings, could boost the therapeutic effect of ICB while alleviating the potential side effects. Most importantly, the application of FUS to ultrasound-sensitive small particles, such as microbubbles (MBs) or nanoparticles (NPs), allows for precise delivery and release of genetic materials, catalysts and chemotherapeutic agents to tumor sites, thus enhancing the anti-tumor effects of ICB while minimizing toxicity. In this...
In the last decade, immune checkpoint blockade (ICB) has revolutionized the standard of treatment... more In the last decade, immune checkpoint blockade (ICB) has revolutionized the standard of treatment for solid tumors. Despite success in several immunogenic tumor types evidenced by improved survival, ICB remains largely unresponsive, especially in “cold tumors” with poor lymphocyte infiltration. In addition, side effects such as immune-related adverse events (irAEs) are also obstacles for the clinical translation of ICB. Recent studies have shown that focused ultrasound (FUS), a non-invasive technology proven to be effective and safe for tumor treatment in clinical settings, could boost the therapeutic effect of ICB while alleviating the potential side effects. Most importantly, the application of FUS to ultrasound-sensitive small particles, such as microbubbles (MBs) or nanoparticles (NPs), allows for precise delivery and release of genetic materials, catalysts and chemotherapeutic agents to tumor sites, thus enhancing the anti-tumor effects of ICB while minimizing toxicity. In this...
BackgroundMany modifications to fixed orthodontic appliances have been introduced to manage biofi... more BackgroundMany modifications to fixed orthodontic appliances have been introduced to manage biofilm formation. The aim of this review was to investigate elastomeric ligation in comparison with stainless steel ligation and self‐ligation with regard to microbiological and clinical indicators of biofilm formation in patients wearing multi‐bracketed fixed orthodontic appliances.MethodsThe MEDLINE and the EMBASE databases were searched up to February 2021 and supplemented by additional manual searches of bibliographies. Parallel‐group and split‐mouth randomized controlled trials (RCTs) comparing different ligation methods were identified. The Cochrane Risk of Bias‐2 tool was applied to assess the quality of evidence.ResultsA total of 11 RCTs were included in this review. Nine RCTs compared self‐ligation and elastomeric ligation; two compared elastomeric ligation and stainless steel ligation. The included studies had either some concerns or were at a high risk of bias. Qualitative assessm...
OBJECTIVES To examine the relationship between masticatory muscle activity (MMA), self-reported o... more OBJECTIVES To examine the relationship between masticatory muscle activity (MMA), self-reported oral behaviours (OBs) and overall physical activity (PA) in adult women. MATERIALS AND METHODS MMA and PA were assessed by a wearable electromyography (EMG) device and accelerometer respectively, worn over 2 non-consecutive days by 53 women (mean age 27.5 ± 6.4 years). Following the second recording day, self-reported OBs were assessed. MMA was assessed by the number, amplitude and duration of masseter contraction episodes. Masseter muscle EMG outcome measures were number of contraction episodes per hour (CEs/h) and the relative contraction time (RCT%). PA was assessed by time accumulated in moderate to vigorous physical activity (MVPA) and 10-min bouts of MVPA per hour. Data were analysed using mixed model analysis. RESULTS MMA in free-living conditions consisted mostly of low-amplitude (<10% maximum voluntary clenching) and short-duration (<10 s) contraction episodes. Masseter CEs/h were not associated with self-reported levels of OB. Masseter CEs/h were positively associated with time accumulated in MVPA (F = 9.9; p = 0.002) and negatively associated with 10-min bouts of MVPA/h (F = 15.8; p <0.001). RCT% was not significantly associated with either. CONCLUSIONS Objectively assessed MMA is not associated with self-reported OB in free-moving adult females. Moderate to vigorous exercise and physical inactivity are accompanied with an increase in the number of masseter muscle contractions and thus possibly tooth clenching activity. CLINICAL RELEVANCE OB can be influenced by the type and extent of PA. Subjective assessment of MMA by questionnaire and/or interviews may be invalid.
BackgroundGestational diabetes mellitus (GDM) is a metabolic condition defined as glucose intoler... more BackgroundGestational diabetes mellitus (GDM) is a metabolic condition defined as glucose intolerance with first presentation during pregnancy. Many studies suggest that environmental exposures, including air pollution, contribute to the pathogenesis of GDM. Although hair metabolite profiles have been shown to reflect pollution exposure, few studies have examined the link between environmental exposures, the maternal hair metabolome and GDM. The aim of this study was to investigate the longitudinal relationship (from pre-conception through to the third trimester) between air pollution exposure, the hair metabolome and GDM in a Chinese cohort.MethodsA total of 1020 women enrolled in the Complex Lipids in Mothers and Babies (CLIMB) birth cohort were included in our study. Metabolites from maternal hair segments collected pre-conception, and in the first, second, and third trimesters were analysed using gas chromatography-mass spectrometry (GC-MS). Maternal exposure to air pollution wa...
Proteins catalysing the transport of molecules across biological membranes are vital for organism... more Proteins catalysing the transport of molecules across biological membranes are vital for organisms in all kingdoms of life. These proteins are needed for the uptake of nutrients and the efflux of signalling molecules and toxic compounds. In the human opportunistic pathogen Candida albicans, efflux proteins can translocate antifungal drugs, such as fluconazole, and confer drug resistance. There are two main families of membrane proteins involved in drug transport, the major facilitator superfamily (MFS) and the ATP-binding cassette (ABC) proteins. Both types of protein possess multiple membrane spanning α-helices in transmembrane domains (TMDs), and ABC proteins, in addition, contain cytosolic nucleotide-binding domains (NBDs) involved in ATP hydrolysis. ABC proteins, and to a lesser extent MFS proteins, have broad substrate specificities that are determined by the structure and arrangement of the transmembrane α-helices. The multidrug transporter most often associated with drug resistance of C. albicans clinical isolates is ABC protein Cdr1. This is a pleiotropic drug resistance (PDR) ABC protein with domain arrangement NBD1-TMD1-NBD2-TMD2 and unique large extracellular loops between transmembrane α-helices that may be important for pump function. There is no crystal structure for Cdr1, but X-ray structures of related proteins indicate that unique interactions between conserved elements of the TMDs and the NBDs are important for pump function.
The successful biochemical and biophysical characterization of ABC transporters depends heavily o... more The successful biochemical and biophysical characterization of ABC transporters depends heavily on the choice of the heterologous expression system. Over the past two decades, we have developed a yeast membrane protein expression platform that has been used to study many important fungal membrane proteins. The expression host Saccharomyces cerevisiae ADΔΔ is deleted in seven major endogenous ABC transporters and it contains the transcription factor Pdr1-3 with a gain-of-function mutation that enables the constitutive overexpression of heterologous membrane protein genes stably integrated as single copies at the genomic PDR5 locus. The creation of versatile plasmid vectors and the optimization of one-step cloning strategies enables the rapid and accurate cloning, mutagenesis, and expression of heterologous ABC transporters. Here, we describe the development and use of a novel protease-cleavable mGFPHis double tag (i.e., the monomeric yeast enhanced green fluorescent protein yEGFP3 fused to a six-histidine affinity purification tag) that was designed to avoid possible interference of the tag with the protein of interest and to increase the binding efficiency of the His tag to nickel-affinity resins. The fusion of mGFPHis to the membrane protein ORF (open reading frame) enables easy quantification of the protein by inspection of polyacrylamide gels and detection of degradation products retaining the mGFPHis tag. We demonstrate how this feature facilitates detergent screening for membrane protein solubilization. A protocol for the efficient, fast, and reliable isolation of the small-scale plasma membrane preparations of the C-terminally tagged Candida albicans multidrug efflux transporter Cdr1 overexpressed in S. cerevisiae ADΔΔ, is presented. This small-scale plasma membrane isolation protocol generates high-quality plasma membranes within a single working day. The plasma membrane preparations can be used to determine the enzyme activities of Cdr1 and Cdr1 mutant variants.
IntroductionEarly detection of coronavirus disease 2019 (COVID‐19) is paramount for controlling t... more IntroductionEarly detection of coronavirus disease 2019 (COVID‐19) is paramount for controlling the progression and spread of the disease. Currently, nasopharyngeal swabbing (NPS) is the standard method for collecting specimens. Saliva was recently proposed as an easy and safe option with many authorities adopting the methodology despite the limited evidence of efficacy.ObjectivesThe aim of this review was to systematically evaluate the current literature on the use of saliva test for detecting severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and carry out a meta‐analysis to determine its diagnostic accuracy.Materials and methodsProspective studies were searched for in electronic databases, complemented by hand‐searching relevant journals. The risk of bias and applicability were assessed using the revised Quality Assessment of Studies of Diagnostic Accuracy Studies (QUADAS‐2) tool. Meta‐analyses and meta‐regression modeling were performed to calculate the diagnostic accu...
The aim was to investigate the relationship between groups of bacteria identified by cluster anal... more The aim was to investigate the relationship between groups of bacteria identified by cluster analysis of the DGGE fingerprints and the amounts and diversity of yeast present. Bacterial and yeast populations in saliva samples from 24 adults were analysed using denaturing gradient gel electrophoresis (DGGE) of the bacteria present and by yeast culture. Eubacterial DGGE banding patterns showed considerable variation between individuals. Seventy one different amplicon bands were detected, the band number per saliva sample ranged from 21 to 39 (mean±SD=29.3±4.9). Cluster and principal component analysis of the bacterial DGGE patterns yielded three major clusters containing 20 of the samples. Seventeen of the 24 (71%) saliva samples were yeast positive with concentrations up to 10(3)cfu/mL. Candida albicans was the predominant species in saliva samples although six other yeast species, including Candida dubliniensis, Candida tropicalis, Candida krusei, Candida guilliermondii, Candida rugo...
Candida albicans is an opportunistic fungus which causes both superficial infections and life-thr... more Candida albicans is an opportunistic fungus which causes both superficial infections and life-threatening systemic candidiasis in immunocompromised hosts such as AIDS patients, people with cancer, or other immunosuppressed individuals. Virulence factors for this fungus include the ability to adhere to host tissues, production of tissue damaging secreted enzymes, and changes in morphological form that may enhance tissue penetration and avoidance of immune surveillance. Treatment of candidiasis patients is hampered by a limited choice of antifungal agents and the appearance of clinical isolates resistant to azole drugs. Proteome analysis involves the separation and isolation of proteins by two-dimensional gel electrophoresis and their identification and characterization by mass spectrometry. The systematic application of this methodology to C. albicans is in its infancy, but is progressing rapidly. Comparing protein profiles between avirulent and virulent C. albicans strains, between drug-sensitive and -resistant strains, or between different morphological forms, could identify key control and effector proteins. There are difficulties, however, associated with the display of low abundance and cell envelope-associated proteins and the choice of conditions for obtaining suitable C. albicans cells. This article describes the potential of applying proteome analysis to C. albicans in order to better understand pathogenicity and identify new antifungal targets.
ATP-binding cassette (ABC) proteins are ubiquitous in prokaryotes and eukaryotes. They are involv... more ATP-binding cassette (ABC) proteins are ubiquitous in prokaryotes and eukaryotes. They are involved in energy-dependent transport of molecules across membranes. ABC proteins are often promiscuous transporters that can translocate a variety of substrates. In oral fungi, especially in Candida species, they have been implicated as major contributors to the high-level azole resistance of clinical isolates from infections that do not respond to drug therapy. Although this is predominantly due to efflux of azoles from the cells, ABC proteins can contribute to fungal drug resistance in other ways as well. Cells in biofilms are notoriously resistant to antifungal agents. ABC proteins can contribute to this resistance through the efflux of drugs. Biofilms are complex communities of myriad microorganisms which, to survive in such a milieu, need to communicate with, and respond to, other microorganisms and their products. ABC proteins are involved in the secretion of fungal mating factors and quorum sensing molecules. These molecules affect biofilm structure and behavior that can result in increased drug resistance. Hence, ABC proteins make multiple contributions to oral fungal drug resistance through a variety of responses to environmental signals.
In the last decade, immune checkpoint blockade (ICB) has revolutionized the standard of treatment... more In the last decade, immune checkpoint blockade (ICB) has revolutionized the standard of treatment for solid tumors. Despite success in several immunogenic tumor types evidenced by improved survival, ICB remains largely unresponsive, especially in “cold tumors” with poor lymphocyte infiltration. In addition, side effects such as immune-related adverse events (irAEs) are also obstacles for the clinical translation of ICB. Recent studies have shown that focused ultrasound (FUS), a non-invasive technology proven to be effective and safe for tumor treatment in clinical settings, could boost the therapeutic effect of ICB while alleviating the potential side effects. Most importantly, the application of FUS to ultrasound-sensitive small particles, such as microbubbles (MBs) or nanoparticles (NPs), allows for precise delivery and release of genetic materials, catalysts and chemotherapeutic agents to tumor sites, thus enhancing the anti-tumor effects of ICB while minimizing toxicity. In this...
In the last decade, immune checkpoint blockade (ICB) has revolutionized the standard of treatment... more In the last decade, immune checkpoint blockade (ICB) has revolutionized the standard of treatment for solid tumors. Despite success in several immunogenic tumor types evidenced by improved survival, ICB remains largely unresponsive, especially in “cold tumors” with poor lymphocyte infiltration. In addition, side effects such as immune-related adverse events (irAEs) are also obstacles for the clinical translation of ICB. Recent studies have shown that focused ultrasound (FUS), a non-invasive technology proven to be effective and safe for tumor treatment in clinical settings, could boost the therapeutic effect of ICB while alleviating the potential side effects. Most importantly, the application of FUS to ultrasound-sensitive small particles, such as microbubbles (MBs) or nanoparticles (NPs), allows for precise delivery and release of genetic materials, catalysts and chemotherapeutic agents to tumor sites, thus enhancing the anti-tumor effects of ICB while minimizing toxicity. In this...
BackgroundMany modifications to fixed orthodontic appliances have been introduced to manage biofi... more BackgroundMany modifications to fixed orthodontic appliances have been introduced to manage biofilm formation. The aim of this review was to investigate elastomeric ligation in comparison with stainless steel ligation and self‐ligation with regard to microbiological and clinical indicators of biofilm formation in patients wearing multi‐bracketed fixed orthodontic appliances.MethodsThe MEDLINE and the EMBASE databases were searched up to February 2021 and supplemented by additional manual searches of bibliographies. Parallel‐group and split‐mouth randomized controlled trials (RCTs) comparing different ligation methods were identified. The Cochrane Risk of Bias‐2 tool was applied to assess the quality of evidence.ResultsA total of 11 RCTs were included in this review. Nine RCTs compared self‐ligation and elastomeric ligation; two compared elastomeric ligation and stainless steel ligation. The included studies had either some concerns or were at a high risk of bias. Qualitative assessm...
OBJECTIVES To examine the relationship between masticatory muscle activity (MMA), self-reported o... more OBJECTIVES To examine the relationship between masticatory muscle activity (MMA), self-reported oral behaviours (OBs) and overall physical activity (PA) in adult women. MATERIALS AND METHODS MMA and PA were assessed by a wearable electromyography (EMG) device and accelerometer respectively, worn over 2 non-consecutive days by 53 women (mean age 27.5 ± 6.4 years). Following the second recording day, self-reported OBs were assessed. MMA was assessed by the number, amplitude and duration of masseter contraction episodes. Masseter muscle EMG outcome measures were number of contraction episodes per hour (CEs/h) and the relative contraction time (RCT%). PA was assessed by time accumulated in moderate to vigorous physical activity (MVPA) and 10-min bouts of MVPA per hour. Data were analysed using mixed model analysis. RESULTS MMA in free-living conditions consisted mostly of low-amplitude (<10% maximum voluntary clenching) and short-duration (<10 s) contraction episodes. Masseter CEs/h were not associated with self-reported levels of OB. Masseter CEs/h were positively associated with time accumulated in MVPA (F = 9.9; p = 0.002) and negatively associated with 10-min bouts of MVPA/h (F = 15.8; p <0.001). RCT% was not significantly associated with either. CONCLUSIONS Objectively assessed MMA is not associated with self-reported OB in free-moving adult females. Moderate to vigorous exercise and physical inactivity are accompanied with an increase in the number of masseter muscle contractions and thus possibly tooth clenching activity. CLINICAL RELEVANCE OB can be influenced by the type and extent of PA. Subjective assessment of MMA by questionnaire and/or interviews may be invalid.
BackgroundGestational diabetes mellitus (GDM) is a metabolic condition defined as glucose intoler... more BackgroundGestational diabetes mellitus (GDM) is a metabolic condition defined as glucose intolerance with first presentation during pregnancy. Many studies suggest that environmental exposures, including air pollution, contribute to the pathogenesis of GDM. Although hair metabolite profiles have been shown to reflect pollution exposure, few studies have examined the link between environmental exposures, the maternal hair metabolome and GDM. The aim of this study was to investigate the longitudinal relationship (from pre-conception through to the third trimester) between air pollution exposure, the hair metabolome and GDM in a Chinese cohort.MethodsA total of 1020 women enrolled in the Complex Lipids in Mothers and Babies (CLIMB) birth cohort were included in our study. Metabolites from maternal hair segments collected pre-conception, and in the first, second, and third trimesters were analysed using gas chromatography-mass spectrometry (GC-MS). Maternal exposure to air pollution wa...
Proteins catalysing the transport of molecules across biological membranes are vital for organism... more Proteins catalysing the transport of molecules across biological membranes are vital for organisms in all kingdoms of life. These proteins are needed for the uptake of nutrients and the efflux of signalling molecules and toxic compounds. In the human opportunistic pathogen Candida albicans, efflux proteins can translocate antifungal drugs, such as fluconazole, and confer drug resistance. There are two main families of membrane proteins involved in drug transport, the major facilitator superfamily (MFS) and the ATP-binding cassette (ABC) proteins. Both types of protein possess multiple membrane spanning α-helices in transmembrane domains (TMDs), and ABC proteins, in addition, contain cytosolic nucleotide-binding domains (NBDs) involved in ATP hydrolysis. ABC proteins, and to a lesser extent MFS proteins, have broad substrate specificities that are determined by the structure and arrangement of the transmembrane α-helices. The multidrug transporter most often associated with drug resistance of C. albicans clinical isolates is ABC protein Cdr1. This is a pleiotropic drug resistance (PDR) ABC protein with domain arrangement NBD1-TMD1-NBD2-TMD2 and unique large extracellular loops between transmembrane α-helices that may be important for pump function. There is no crystal structure for Cdr1, but X-ray structures of related proteins indicate that unique interactions between conserved elements of the TMDs and the NBDs are important for pump function.
The successful biochemical and biophysical characterization of ABC transporters depends heavily o... more The successful biochemical and biophysical characterization of ABC transporters depends heavily on the choice of the heterologous expression system. Over the past two decades, we have developed a yeast membrane protein expression platform that has been used to study many important fungal membrane proteins. The expression host Saccharomyces cerevisiae ADΔΔ is deleted in seven major endogenous ABC transporters and it contains the transcription factor Pdr1-3 with a gain-of-function mutation that enables the constitutive overexpression of heterologous membrane protein genes stably integrated as single copies at the genomic PDR5 locus. The creation of versatile plasmid vectors and the optimization of one-step cloning strategies enables the rapid and accurate cloning, mutagenesis, and expression of heterologous ABC transporters. Here, we describe the development and use of a novel protease-cleavable mGFPHis double tag (i.e., the monomeric yeast enhanced green fluorescent protein yEGFP3 fused to a six-histidine affinity purification tag) that was designed to avoid possible interference of the tag with the protein of interest and to increase the binding efficiency of the His tag to nickel-affinity resins. The fusion of mGFPHis to the membrane protein ORF (open reading frame) enables easy quantification of the protein by inspection of polyacrylamide gels and detection of degradation products retaining the mGFPHis tag. We demonstrate how this feature facilitates detergent screening for membrane protein solubilization. A protocol for the efficient, fast, and reliable isolation of the small-scale plasma membrane preparations of the C-terminally tagged Candida albicans multidrug efflux transporter Cdr1 overexpressed in S. cerevisiae ADΔΔ, is presented. This small-scale plasma membrane isolation protocol generates high-quality plasma membranes within a single working day. The plasma membrane preparations can be used to determine the enzyme activities of Cdr1 and Cdr1 mutant variants.
IntroductionEarly detection of coronavirus disease 2019 (COVID‐19) is paramount for controlling t... more IntroductionEarly detection of coronavirus disease 2019 (COVID‐19) is paramount for controlling the progression and spread of the disease. Currently, nasopharyngeal swabbing (NPS) is the standard method for collecting specimens. Saliva was recently proposed as an easy and safe option with many authorities adopting the methodology despite the limited evidence of efficacy.ObjectivesThe aim of this review was to systematically evaluate the current literature on the use of saliva test for detecting severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and carry out a meta‐analysis to determine its diagnostic accuracy.Materials and methodsProspective studies were searched for in electronic databases, complemented by hand‐searching relevant journals. The risk of bias and applicability were assessed using the revised Quality Assessment of Studies of Diagnostic Accuracy Studies (QUADAS‐2) tool. Meta‐analyses and meta‐regression modeling were performed to calculate the diagnostic accu...
The aim was to investigate the relationship between groups of bacteria identified by cluster anal... more The aim was to investigate the relationship between groups of bacteria identified by cluster analysis of the DGGE fingerprints and the amounts and diversity of yeast present. Bacterial and yeast populations in saliva samples from 24 adults were analysed using denaturing gradient gel electrophoresis (DGGE) of the bacteria present and by yeast culture. Eubacterial DGGE banding patterns showed considerable variation between individuals. Seventy one different amplicon bands were detected, the band number per saliva sample ranged from 21 to 39 (mean±SD=29.3±4.9). Cluster and principal component analysis of the bacterial DGGE patterns yielded three major clusters containing 20 of the samples. Seventeen of the 24 (71%) saliva samples were yeast positive with concentrations up to 10(3)cfu/mL. Candida albicans was the predominant species in saliva samples although six other yeast species, including Candida dubliniensis, Candida tropicalis, Candida krusei, Candida guilliermondii, Candida rugo...
Candida albicans is an opportunistic fungus which causes both superficial infections and life-thr... more Candida albicans is an opportunistic fungus which causes both superficial infections and life-threatening systemic candidiasis in immunocompromised hosts such as AIDS patients, people with cancer, or other immunosuppressed individuals. Virulence factors for this fungus include the ability to adhere to host tissues, production of tissue damaging secreted enzymes, and changes in morphological form that may enhance tissue penetration and avoidance of immune surveillance. Treatment of candidiasis patients is hampered by a limited choice of antifungal agents and the appearance of clinical isolates resistant to azole drugs. Proteome analysis involves the separation and isolation of proteins by two-dimensional gel electrophoresis and their identification and characterization by mass spectrometry. The systematic application of this methodology to C. albicans is in its infancy, but is progressing rapidly. Comparing protein profiles between avirulent and virulent C. albicans strains, between drug-sensitive and -resistant strains, or between different morphological forms, could identify key control and effector proteins. There are difficulties, however, associated with the display of low abundance and cell envelope-associated proteins and the choice of conditions for obtaining suitable C. albicans cells. This article describes the potential of applying proteome analysis to C. albicans in order to better understand pathogenicity and identify new antifungal targets.
ATP-binding cassette (ABC) proteins are ubiquitous in prokaryotes and eukaryotes. They are involv... more ATP-binding cassette (ABC) proteins are ubiquitous in prokaryotes and eukaryotes. They are involved in energy-dependent transport of molecules across membranes. ABC proteins are often promiscuous transporters that can translocate a variety of substrates. In oral fungi, especially in Candida species, they have been implicated as major contributors to the high-level azole resistance of clinical isolates from infections that do not respond to drug therapy. Although this is predominantly due to efflux of azoles from the cells, ABC proteins can contribute to fungal drug resistance in other ways as well. Cells in biofilms are notoriously resistant to antifungal agents. ABC proteins can contribute to this resistance through the efflux of drugs. Biofilms are complex communities of myriad microorganisms which, to survive in such a milieu, need to communicate with, and respond to, other microorganisms and their products. ABC proteins are involved in the secretion of fungal mating factors and quorum sensing molecules. These molecules affect biofilm structure and behavior that can result in increased drug resistance. Hence, ABC proteins make multiple contributions to oral fungal drug resistance through a variety of responses to environmental signals.
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