Oral warts, caused by human papillomavirus (HPV), and oral hairy leukoplakia (OHL) caused by Epst... more Oral warts, caused by human papillomavirus (HPV), and oral hairy leukoplakia (OHL) caused by Epstein-Barr virus (EBV), are common oral manifestations in HIV-infected persons. Although both conditions occur most often with reduced blood CD4+ T-cell numbers, oral warts and OHL rarely occur simultaneously, suggesting that dysfunctions in other secondary local immune parameters are also involved. The present study evaluated tissue-associated proinflammatory and T-helper cytokine and chemokine mRNA expression and the presence of T cells in each lesion. Biopsies were taken from lesion-positive and adjacent lesion-negative sites of HIV+ persons with oral warts or OHL and lesion-negative sites from HIV+ persons who were oral HPV or EBV DNA-positive (matched controls). Cytokine/chemokine mRNA expression was quantified by real-time polymerase chain reaction. CD3, CD4, and CD8 cells were identified by immunohistochemistry. No differences were detected in tissue-associated cytokine/chemokine mRNA expression in warts or OHL when compared to lesion-negative sites. Immunohistochemical analysis of T cells showed CD8+ cells exclusively, but few cells were present in either lesion. No differences were detected between lesion-positive and -negative control sites of each pathologic condition. Little evidence was found for local immune reactivity to either oral warts and OHL, suggesting that CD4+ T cells are a primary host defense against both oral warts and OHL, but with nonimmune factors potentially responsible for the divergent prevalence of each.
Murine vaginitis model. A condition of pseudoestrus is required to obtain a persistent vaginal ye... more Murine vaginitis model. A condition of pseudoestrus is required to obtain a persistent vaginal yeast infection in rodents. Mice were injected subcutaneously (under manual restraining) with 1.0 mg estradiol valerate dissolved in sesame oil 3 days prior to and 4 days after vaginal inoculation. On the day prior to inoculation, a blastospore culture of C. albicans 3153A was prepared. On the day of infection, blastospores were collected and washed once with phosphate-buffered saline (PBS) and resuspended at 2.5 x 106/ml in PBS for an inoculum of 5x104 cell/ 0.02 ml PBS for each infection. For inoculation, animals were anesthetized “to effect” by isoflurane inhalation. To anesthetized animals, 5 x 104 C. albicans 3153A blastospores in 20 l PBS was introduced into the vagina, using a pipetman. Once-daily oral gavage treatments of 4, 10, and 25 mg/kg VT-1161, 25 mg/kg FLU, or vehicle (20% cremaphor EL) began on day 3 post-inoculation and continued through day 6 (10 animals per group). On da...
Trained innate immunity (TII) is induced following immunization with live attenuated microbes and... more Trained innate immunity (TII) is induced following immunization with live attenuated microbes and represents a clinically important strategy to enhance innate defenses. TII was initially demonstrated following intravenous inoculation with low-virulence Candida albicans , with protection against a subsequent lethal C. albicans intravenous bloodstream infection (BSI) mediated by monocytes with enhanced cytokine responses.
Our laboratory recently reported that the EP4receptor antagonist, L-161,982, had direct growth-in... more Our laboratory recently reported that the EP4receptor antagonist, L-161,982, had direct growth-inhibitory effects onStaphylococcus aureus in vitroand in vivo, reducing microbial burden and providing significant protection against lethality in models ofS. aureusmonomicrobial and polymicrobial intra-abdominal infection. This antimicrobial activity was observed with both methicillin-sensitive and methicillin-resistantS. aureus(MRSA), as well as other Gram-positive bacteria. The antimicrobial activity of L-161,982 was independent of EP4receptor inhibitory activity. In this study, we investigated the mechanism of action (MOA) of L-161,982, which contains a sulfonamide functional group. However, results demonstrate L-161,982 does not affect folate synthesis (sulfonamide MOA), oxidative stress, or membrane permeability. Instead, our results suggest that the inhibitor works via effects on inhibition of the electron transport chain (ETC). Similar to other ETC inhibitors, L-161,982 exposure r...
Persons infected with HIV are particularly vulnerable to a variety of oral microbial diseases. Al... more Persons infected with HIV are particularly vulnerable to a variety of oral microbial diseases. Although various study designs and detection approaches have been used to compare the oral microbiota of HIV-negative and HIV-positive persons, both with and without highly active antiretroviral therapy (HAART), methods have varied, and results have not been consistent or conclusive. The purpose of the present study was to compare the oral bacterial community composition in HIV-positive persons under HAART to an HIV-negative group using 16S rRNA gene sequence analysis. Extensive clinical data was collected, and efforts were made to balance the groups on clinical variables to minimize confounding. Multivariate analysis was used to assess the independent contribution of HIV status. Eighty-nine HIV-negative participants and 252 HIV-positive participants under HAART were sampled. The independent effect of HIV under HAART on the oral microbiome was statistically significant, but smaller than th...
Polymicrobial intra-abdominal infections (IAI) are clinically prevalent and cause significant mor... more Polymicrobial intra-abdominal infections (IAI) are clinically prevalent and cause significant morbidity and mortality, especially those involving fungi. Our laboratory developed a mouse model of polymicrobial IAI and demonstrated that coinfection with Candida albicans and Staphylococcus aureus ( C. albicans / S. aureus ) results in 80 to 90% mortality in 48 to 72 h due to robust local and systemic inflammation.
Antimicrobial agents and chemotherapy, Jan 29, 2018
is an important opportunistic pathogen causing various human infections that are often treated wi... more is an important opportunistic pathogen causing various human infections that are often treated with azole antifungals. The US CDC now regards developing candidal antifungal resistance as a threat, creating a need for new and more effective antifungal treatments. Iron is an essential nutrient for all living cells and there is growing evidence that interference with iron homeostasis of can improve its response to antifungals. This study was aimed at establishing whether withholding iron by currently used medical iron chelators and the novel chelator DIBI could restrict growth and also enhance the activity of azoles against clinical isolates of DIBI but not deferoxamine or deferiprone, inhibited growth of at relatively low concentrations and this inhibition was reversed by iron addition. DIBI in combination with various azoles demonstrated stronger growth inhibition than the azoles alone and greatly prolonged inhibition of cell multiplication. In addition, administration of DIBI along ...
Polymicrobial intra-abdominal infections (IAIs) are clinically prevalent and cause significant mo... more Polymicrobial intra-abdominal infections (IAIs) are clinically prevalent and cause significant morbidity and mortality, especially those involving fungi. Our laboratory developed a mouse model of IAI and demonstrated that intraperitoneal inoculation withor other virulent non-(NAC) species plusresulted in 70 to 80% mortality in 48 to 72 h due to robust local and systemic inflammation (sepsis). Surprisingly, inoculation withorwithresulted in minimal mortality, and rechallenge of these mice with lethal/(i.e., coninfection) resulted in >90% protection. The purpose of this study was to define requirements for/-mediated protection and interrogate the mechanism of the protective response. Protection was conferred byalone or by killedplus livealone was not protective, and killedcompromised-induced protection./also protected against lethal challenge by NAC plusand could protect for a long-term duration (60 days between primary challenge andrechallenge). Unexpectedly, mice deficient in T a...
Antimicrobial agents and chemotherapy, Apr 1, 2017
The fungal pathogen Candida albicans causes a variety of oral infections, including denture stoma... more The fungal pathogen Candida albicans causes a variety of oral infections, including denture stomatitis, which is characterized by inflammation of the oral mucosa in direct contact with dentures and affects a significant number of otherwise healthy denture wearers. While antifungal treatment reduces symptoms, infections are often recurrent. One strategy to address this problem is to incorporate compounds with fungicidal activities into denture materials to prevent colonization. Our laboratory synthesized novel derivatives of 1,4-diazabicyclo[2.2.2]octane (DABCO), which is an organic compound typically used as a catalyst in polymerization reactions. DABCO derivatives with different aliphatic chain lengths (DC16, DC16F, DC18, and C6DC16), as well as methacrylate monomers conjugated to DABCO compounds (DC11MAF and C2DC11MAF), were synthesized and tested for antimicrobial activity. All the compounds exhibited fungicidal activity against several Candida species at concentrations ranging b...
Proceedings of the National Academy of Sciences, 2013
Infection by pathogenic fungi, such as Candida albicans , begins with adhesion to host cells or i... more Infection by pathogenic fungi, such as Candida albicans , begins with adhesion to host cells or implanted medical devices followed by biofilm formation. By high-throughput phenotypic screening of small molecules, we identified compounds that inhibit adhesion of C. albicans to polystyrene. Our lead candidate compound also inhibits binding of C. albicans to cultured human epithelial cells, the yeast-to-hyphal morphological transition, induction of the hyphal-specific HWP1 promoter, biofilm formation on silicone elastomers, and pathogenesis in a nematode infection model as well as alters fungal morphology in a mouse mucosal infection assay. We term this compound filastatin based on its strong inhibition of filamentation, and we use chemical genetic experiments to show that it acts downstream of multiple signaling pathways. These studies show that high-throughput functional assays targeting fungal adhesion can provide chemical probes for study of multiple aspects of fungal pathogenesis.
In HIV+ persons with reduced CD4+ T cells, oropharyngeal candidiasis (OPC) is often associated wi... more In HIV+ persons with reduced CD4+ T cells, oropharyngeal candidiasis (OPC) is often associated with the accumulation of CD8+ T cells at the epithelial/lamina propria interface within the lesion together with increased tissue-associated cytokines and chemokines. Despite this reactivity, a dysfunction in the ability of the CD8+ cells to reach the organism at the outer epithelium is postulated. The purpose of this study was to examine chemokine receptors present in the OPC lesions for a potential role in susceptibility to infection. Biopsies taken from buccal mucosa of HIV- persons, healthy mucosa of HIV+ OPC- persons, and OPC lesions were processed for protein immunohistochemical staining or RNA analysis by real-time PCR and Superarray. There was little change in expression of chemokine receptors at the protein or RNA level between OPC+ and OPC- tissue. At the protein level, increases occurred in OPC+ persons only if associated with CD8 cells. In the Superarray, of the 22 chemokine receptor mRNAs expressed, c. 90% remained unchanged (< 1.0-fold change) between HIV- and HIV+ tissue and between HIV+ OPC- and HIV+ OPC+ tissue. Tissue-associated chemokine receptor expression does not appear to contribute to the dysfunction in cellular migration associated with susceptibility to OPC.
Oropharyngeal candidiasis (OPC), caused by Candida albicans, is the most common oral infection in... more Oropharyngeal candidiasis (OPC), caused by Candida albicans, is the most common oral infection in HIV(+) persons. Oral epithelial cells are considered important for innate host defense against OPC with production of cytokines in response to C. albicans and the ability to inhibit Candida growth in vitro. The purpose of this study was to determine if Candida similarly induces cytokines by oral epithelial cells from HIV(+) persons, including those with OPC, as well as to determine if cytokines can influence the oral epithelial cell anti-Candida activity. Supernatants from oral epithelial cells from HIV(+) persons with and without OPC cultured with Candida were evaluated for cytokines by ELISA, or cytokines were added to the standard growth inhibition assay using epithelial cells from HIV(-) persons. Results showed low Candida-induced epithelial cell cytokine production from HIV(+) persons, but with some elevated proinflammatory cytokines (TNF-alpha, IL-6) in those with OPC compared to those without OPC. The addition of specific proinflammatory or Th cytokines had no effect on oral epithelial cell anti-Candida activity in healthy HIV(-) persons. These results suggest that oral epithelial cells from HIV(+) persons can contribute at some level to the oral cytokine milieu in response to Candida during OPC, but that cytokines do not appear to influence oral epithelial cell anti-Candida activity.
Current understanding of resistance and susceptibility to vulvovaginal candidiasis challenges exi... more Current understanding of resistance and susceptibility to vulvovaginal candidiasis challenges existing paradigms of host defence against fungal infection. While abiotic biofilm formation has a clearly established role during systemic Candida infections, it is not known whether C. albicans forms biofilms on the vaginal mucosa and the possible role of biofilms in disease. In vivo and ex vivo murine vaginitis models were employed to examine biofilm formation by scanning electron and confocal microscopy. C. albicans strains included 3153A (lab strain), DAY185 (parental control strain), and mutants defective in morphogenesis and/or biofilm formation in vitro (efg1/efg1 and bcr1/bcr1). Both 3153A and DAY815 formed biofilms on the vaginal mucosa in vivo and ex vivo as indicated by high fungal burden and microscopic analysis demonstrating typical biofilm architecture and presence of extracellular matrix (ECM) co-localized with the presence of fungi. In contrast, efg1/efg1 and bcr1/bcr1 muta...
Oral warts, caused by human papillomavirus (HPV), and oral hairy leukoplakia (OHL) caused by Epst... more Oral warts, caused by human papillomavirus (HPV), and oral hairy leukoplakia (OHL) caused by Epstein-Barr virus (EBV), are common oral manifestations in HIV-infected persons. Although both conditions occur most often with reduced blood CD4+ T-cell numbers, oral warts and OHL rarely occur simultaneously, suggesting that dysfunctions in other secondary local immune parameters are also involved. The present study evaluated tissue-associated proinflammatory and T-helper cytokine and chemokine mRNA expression and the presence of T cells in each lesion. Biopsies were taken from lesion-positive and adjacent lesion-negative sites of HIV+ persons with oral warts or OHL and lesion-negative sites from HIV+ persons who were oral HPV or EBV DNA-positive (matched controls). Cytokine/chemokine mRNA expression was quantified by real-time polymerase chain reaction. CD3, CD4, and CD8 cells were identified by immunohistochemistry. No differences were detected in tissue-associated cytokine/chemokine mRNA expression in warts or OHL when compared to lesion-negative sites. Immunohistochemical analysis of T cells showed CD8+ cells exclusively, but few cells were present in either lesion. No differences were detected between lesion-positive and -negative control sites of each pathologic condition. Little evidence was found for local immune reactivity to either oral warts and OHL, suggesting that CD4+ T cells are a primary host defense against both oral warts and OHL, but with nonimmune factors potentially responsible for the divergent prevalence of each.
Murine vaginitis model. A condition of pseudoestrus is required to obtain a persistent vaginal ye... more Murine vaginitis model. A condition of pseudoestrus is required to obtain a persistent vaginal yeast infection in rodents. Mice were injected subcutaneously (under manual restraining) with 1.0 mg estradiol valerate dissolved in sesame oil 3 days prior to and 4 days after vaginal inoculation. On the day prior to inoculation, a blastospore culture of C. albicans 3153A was prepared. On the day of infection, blastospores were collected and washed once with phosphate-buffered saline (PBS) and resuspended at 2.5 x 106/ml in PBS for an inoculum of 5x104 cell/ 0.02 ml PBS for each infection. For inoculation, animals were anesthetized “to effect” by isoflurane inhalation. To anesthetized animals, 5 x 104 C. albicans 3153A blastospores in 20 l PBS was introduced into the vagina, using a pipetman. Once-daily oral gavage treatments of 4, 10, and 25 mg/kg VT-1161, 25 mg/kg FLU, or vehicle (20% cremaphor EL) began on day 3 post-inoculation and continued through day 6 (10 animals per group). On da...
Trained innate immunity (TII) is induced following immunization with live attenuated microbes and... more Trained innate immunity (TII) is induced following immunization with live attenuated microbes and represents a clinically important strategy to enhance innate defenses. TII was initially demonstrated following intravenous inoculation with low-virulence Candida albicans , with protection against a subsequent lethal C. albicans intravenous bloodstream infection (BSI) mediated by monocytes with enhanced cytokine responses.
Our laboratory recently reported that the EP4receptor antagonist, L-161,982, had direct growth-in... more Our laboratory recently reported that the EP4receptor antagonist, L-161,982, had direct growth-inhibitory effects onStaphylococcus aureus in vitroand in vivo, reducing microbial burden and providing significant protection against lethality in models ofS. aureusmonomicrobial and polymicrobial intra-abdominal infection. This antimicrobial activity was observed with both methicillin-sensitive and methicillin-resistantS. aureus(MRSA), as well as other Gram-positive bacteria. The antimicrobial activity of L-161,982 was independent of EP4receptor inhibitory activity. In this study, we investigated the mechanism of action (MOA) of L-161,982, which contains a sulfonamide functional group. However, results demonstrate L-161,982 does not affect folate synthesis (sulfonamide MOA), oxidative stress, or membrane permeability. Instead, our results suggest that the inhibitor works via effects on inhibition of the electron transport chain (ETC). Similar to other ETC inhibitors, L-161,982 exposure r...
Persons infected with HIV are particularly vulnerable to a variety of oral microbial diseases. Al... more Persons infected with HIV are particularly vulnerable to a variety of oral microbial diseases. Although various study designs and detection approaches have been used to compare the oral microbiota of HIV-negative and HIV-positive persons, both with and without highly active antiretroviral therapy (HAART), methods have varied, and results have not been consistent or conclusive. The purpose of the present study was to compare the oral bacterial community composition in HIV-positive persons under HAART to an HIV-negative group using 16S rRNA gene sequence analysis. Extensive clinical data was collected, and efforts were made to balance the groups on clinical variables to minimize confounding. Multivariate analysis was used to assess the independent contribution of HIV status. Eighty-nine HIV-negative participants and 252 HIV-positive participants under HAART were sampled. The independent effect of HIV under HAART on the oral microbiome was statistically significant, but smaller than th...
Polymicrobial intra-abdominal infections (IAI) are clinically prevalent and cause significant mor... more Polymicrobial intra-abdominal infections (IAI) are clinically prevalent and cause significant morbidity and mortality, especially those involving fungi. Our laboratory developed a mouse model of polymicrobial IAI and demonstrated that coinfection with Candida albicans and Staphylococcus aureus ( C. albicans / S. aureus ) results in 80 to 90% mortality in 48 to 72 h due to robust local and systemic inflammation.
Antimicrobial agents and chemotherapy, Jan 29, 2018
is an important opportunistic pathogen causing various human infections that are often treated wi... more is an important opportunistic pathogen causing various human infections that are often treated with azole antifungals. The US CDC now regards developing candidal antifungal resistance as a threat, creating a need for new and more effective antifungal treatments. Iron is an essential nutrient for all living cells and there is growing evidence that interference with iron homeostasis of can improve its response to antifungals. This study was aimed at establishing whether withholding iron by currently used medical iron chelators and the novel chelator DIBI could restrict growth and also enhance the activity of azoles against clinical isolates of DIBI but not deferoxamine or deferiprone, inhibited growth of at relatively low concentrations and this inhibition was reversed by iron addition. DIBI in combination with various azoles demonstrated stronger growth inhibition than the azoles alone and greatly prolonged inhibition of cell multiplication. In addition, administration of DIBI along ...
Polymicrobial intra-abdominal infections (IAIs) are clinically prevalent and cause significant mo... more Polymicrobial intra-abdominal infections (IAIs) are clinically prevalent and cause significant morbidity and mortality, especially those involving fungi. Our laboratory developed a mouse model of IAI and demonstrated that intraperitoneal inoculation withor other virulent non-(NAC) species plusresulted in 70 to 80% mortality in 48 to 72 h due to robust local and systemic inflammation (sepsis). Surprisingly, inoculation withorwithresulted in minimal mortality, and rechallenge of these mice with lethal/(i.e., coninfection) resulted in >90% protection. The purpose of this study was to define requirements for/-mediated protection and interrogate the mechanism of the protective response. Protection was conferred byalone or by killedplus livealone was not protective, and killedcompromised-induced protection./also protected against lethal challenge by NAC plusand could protect for a long-term duration (60 days between primary challenge andrechallenge). Unexpectedly, mice deficient in T a...
Antimicrobial agents and chemotherapy, Apr 1, 2017
The fungal pathogen Candida albicans causes a variety of oral infections, including denture stoma... more The fungal pathogen Candida albicans causes a variety of oral infections, including denture stomatitis, which is characterized by inflammation of the oral mucosa in direct contact with dentures and affects a significant number of otherwise healthy denture wearers. While antifungal treatment reduces symptoms, infections are often recurrent. One strategy to address this problem is to incorporate compounds with fungicidal activities into denture materials to prevent colonization. Our laboratory synthesized novel derivatives of 1,4-diazabicyclo[2.2.2]octane (DABCO), which is an organic compound typically used as a catalyst in polymerization reactions. DABCO derivatives with different aliphatic chain lengths (DC16, DC16F, DC18, and C6DC16), as well as methacrylate monomers conjugated to DABCO compounds (DC11MAF and C2DC11MAF), were synthesized and tested for antimicrobial activity. All the compounds exhibited fungicidal activity against several Candida species at concentrations ranging b...
Proceedings of the National Academy of Sciences, 2013
Infection by pathogenic fungi, such as Candida albicans , begins with adhesion to host cells or i... more Infection by pathogenic fungi, such as Candida albicans , begins with adhesion to host cells or implanted medical devices followed by biofilm formation. By high-throughput phenotypic screening of small molecules, we identified compounds that inhibit adhesion of C. albicans to polystyrene. Our lead candidate compound also inhibits binding of C. albicans to cultured human epithelial cells, the yeast-to-hyphal morphological transition, induction of the hyphal-specific HWP1 promoter, biofilm formation on silicone elastomers, and pathogenesis in a nematode infection model as well as alters fungal morphology in a mouse mucosal infection assay. We term this compound filastatin based on its strong inhibition of filamentation, and we use chemical genetic experiments to show that it acts downstream of multiple signaling pathways. These studies show that high-throughput functional assays targeting fungal adhesion can provide chemical probes for study of multiple aspects of fungal pathogenesis.
In HIV+ persons with reduced CD4+ T cells, oropharyngeal candidiasis (OPC) is often associated wi... more In HIV+ persons with reduced CD4+ T cells, oropharyngeal candidiasis (OPC) is often associated with the accumulation of CD8+ T cells at the epithelial/lamina propria interface within the lesion together with increased tissue-associated cytokines and chemokines. Despite this reactivity, a dysfunction in the ability of the CD8+ cells to reach the organism at the outer epithelium is postulated. The purpose of this study was to examine chemokine receptors present in the OPC lesions for a potential role in susceptibility to infection. Biopsies taken from buccal mucosa of HIV- persons, healthy mucosa of HIV+ OPC- persons, and OPC lesions were processed for protein immunohistochemical staining or RNA analysis by real-time PCR and Superarray. There was little change in expression of chemokine receptors at the protein or RNA level between OPC+ and OPC- tissue. At the protein level, increases occurred in OPC+ persons only if associated with CD8 cells. In the Superarray, of the 22 chemokine receptor mRNAs expressed, c. 90% remained unchanged (< 1.0-fold change) between HIV- and HIV+ tissue and between HIV+ OPC- and HIV+ OPC+ tissue. Tissue-associated chemokine receptor expression does not appear to contribute to the dysfunction in cellular migration associated with susceptibility to OPC.
Oropharyngeal candidiasis (OPC), caused by Candida albicans, is the most common oral infection in... more Oropharyngeal candidiasis (OPC), caused by Candida albicans, is the most common oral infection in HIV(+) persons. Oral epithelial cells are considered important for innate host defense against OPC with production of cytokines in response to C. albicans and the ability to inhibit Candida growth in vitro. The purpose of this study was to determine if Candida similarly induces cytokines by oral epithelial cells from HIV(+) persons, including those with OPC, as well as to determine if cytokines can influence the oral epithelial cell anti-Candida activity. Supernatants from oral epithelial cells from HIV(+) persons with and without OPC cultured with Candida were evaluated for cytokines by ELISA, or cytokines were added to the standard growth inhibition assay using epithelial cells from HIV(-) persons. Results showed low Candida-induced epithelial cell cytokine production from HIV(+) persons, but with some elevated proinflammatory cytokines (TNF-alpha, IL-6) in those with OPC compared to those without OPC. The addition of specific proinflammatory or Th cytokines had no effect on oral epithelial cell anti-Candida activity in healthy HIV(-) persons. These results suggest that oral epithelial cells from HIV(+) persons can contribute at some level to the oral cytokine milieu in response to Candida during OPC, but that cytokines do not appear to influence oral epithelial cell anti-Candida activity.
Current understanding of resistance and susceptibility to vulvovaginal candidiasis challenges exi... more Current understanding of resistance and susceptibility to vulvovaginal candidiasis challenges existing paradigms of host defence against fungal infection. While abiotic biofilm formation has a clearly established role during systemic Candida infections, it is not known whether C. albicans forms biofilms on the vaginal mucosa and the possible role of biofilms in disease. In vivo and ex vivo murine vaginitis models were employed to examine biofilm formation by scanning electron and confocal microscopy. C. albicans strains included 3153A (lab strain), DAY185 (parental control strain), and mutants defective in morphogenesis and/or biofilm formation in vitro (efg1/efg1 and bcr1/bcr1). Both 3153A and DAY815 formed biofilms on the vaginal mucosa in vivo and ex vivo as indicated by high fungal burden and microscopic analysis demonstrating typical biofilm architecture and presence of extracellular matrix (ECM) co-localized with the presence of fungi. In contrast, efg1/efg1 and bcr1/bcr1 muta...
Uploads
Papers by Elizabeth Lilly