A novel microbe-drug association prediction model based on graph attention networks and bilayer random forest.

BACKGROUND: In recent years, the extensive use of drugs and antibiotics has led to increasing microbial resistance. Therefore, it becomes crucial to explore deep connections between drugs and microbes. However, traditional biological experiments are very expensive and time-consuming. Therefore, it is meaningful to develop efficient computational models to forecast potential microbe-drug associations. RESULTS: In this manuscript, we proposed a novel prediction model called GARFMDA by combining graph attention networks and bilayer random forest to infer probable microbe-drug correlations. In GARFMDA, through integrating different microbe-drug-disease correlation indices, we constructed two different microbe-drug networks first. And then, based on multiple measures of similarity, we constructed a unique feature matrix for drugs and microbes respectively. Next, we fed these newly-obtained microbe-drug networks together with feature matrices into the graph attention network to extract the low-dimensional feature representations for drugs and microbes separately. Thereafter, these low-dimensional feature representations, along with the feature matrices, would be further inputted into the first layer of the Bilayer random forest model to obtain the contribution values of all features. And then, after removing features with low contribution values, these contribution values would be fed into the second layer of the Bilayer random forest to detect potential links between microbes and drugs. CONCLUSIONS: Experimental results and case studies show that GARFMDA can achieve better prediction performance than state-of-the-art approaches, which means that GARFMDA may be a useful tool in the field of microbe-drug association prediction in the future. Besides, the source code of GARFMDA is available at https://github.com/KuangHaiYue/GARFMDA.git.

Upper respiratory tract mycobiome alterations in different kinds of pulmonary disease.

Introduction: The human respiratory tract is considered to be a polymicrobial niche, and an imbalance in the microorganism composition is normally associated with several respiratory diseases. In addition to the well-studied bacteriome, the existence of fungal species in the respiratory tract has drawn increasing attention and has been suggested to have a significant clinical impact. However, the understanding of the respiratory fungal microbiota (mycobiome) in pulmonary diseases is still insufficient. Methods: In this study, we investigated the fungal community composition of oropharynx swab (OS) samples from patients with five kinds of pulmonary disease, including interstitial lung disease (ILD), bacterial pneumonia (BP), fungal pneumonia (FP), asthma (AS) and lung cancer (LC), and compared them with healthy controls (HCs), based on high-throughput sequencing of the amplified fungal internal transcribed spacer (ITS) region. Results: The results showed significant differences in fungal composition and abundance between disease groups and HCs. Malassezia was the most significant genus, which was much more abundant in pulmonary diseases than in the control. In addition, many common taxa were shared among different disease groups, but differences in taxa abundance and specific species in distinct disease groups were also observed. Based on linear discriminant analysis effect size (LefSe), each group had its characteristic species. Furthermore, some species showed a significant correlation with the patient clinical characteristics. Discussion: Our study deepened our understanding of the respiratory tract mycobiome in some diseases that are less studied and identified the commonalities and differences among different kinds of pulmonary disease. These results would provide the solid basis for further investigation of the association between the mycobiome and pathogenicity of pulmonary diseases.

Proteome-Wide Identification and Functional Analysis of Lysine Crotonylation in Trichophyton rubrum Conidial and Mycelial Stages.

Lysine crotonylation is a newly discovered post-translational modification (PTM) with key roles in various important regulatory pathways. Despite its functional significance, there is limited knowledge about crotonylation in fungi. Trichophyton rubrum is the most common fungal pathogen in human infection and is considered a model organism of dermatophytes and human pathogenic filamentous fungi. In this study, we obtained a proteome-wide crotonylation profile of T. rubrum, leading to the identification of 14,019 crotonylated sites on 3144 proteins. The crotonylated proteins were significantly involved in translation and in various metabolic and biosynthetic processes. Some proteins related to fungal pathogenicity were also found to be targets of crotonylation. In addition, extensive crotonylation was found on histones, suggesting a role in epigenetic regulation. Furthermore, about half of the crotonylated proteins were specific to either the conidial or the mycelial stage, and functional enrichment analysis showed some differences between the two stages. The results suggest that the difference in crotonylation between the two stages is not due to differences in protein abundance. Crosstalk of crotonylation with acetylation, propionylation, and succinylation suggests distinct regulatory roles. This study is the first crotonylation analysis in dermatophytes and human pathogenic filamentous fungi. These results represent a solid foundation for further research on PTM regulatory mechanisms in fungi and should facilitate improved antifungal strategies against these medical important species.

Genome-wide identification and functional analysis of circRNAs in Trichophyton rubrum conidial and mycelial stages.

BACKGROUND: Circular RNAs (circRNAs) are a group of noncoding RNAs that participate in gene expression regulation in various pathways. The essential roles of circRNAs have been revealed in many species. However, knowledge of circRNAs in fungi is still not comprehensive. RESULTS: Trichophyton rubrum (T. rubrum) is considered a model organism of human pathogenic filamentous fungi and dermatophytes. In this study, we performed a genome-wide investigation of circRNAs in T. rubrum based on high-throughput sequencing and ultimately identified 4254 circRNAs. Most of these circRNAs were specific to the conidial or mycelial stage, revealing a developmental stage-specific expression pattern. In addition, 940 circRNAs were significantly differentially expressed between the conidial and mycelial stages. PCR experiments conducted on seven randomly selected differentially expressed (DE-) circRNAs confirmed the circularized structures and relative expression levels of these circRNAs. Based on their genome locations, most circRNAs originated from intergenic regions, unlike those in plants and animals. Furthermore, we constructed circRNA-miRNA-mRNA regulatory networks that included 661 DE-circRNAs targeting 140 miRNAs and further regulating 2753 mRNAs. The relative expression levels of two randomly selected circRNA-miRNA-mRNA axes were investigated by qRT-PCR, and the competing endogenous RNA (ceRNA) network theory was validated. Functional enrichment analysis of the target genes suggested that they were significantly involved in posttranscriptional processes and protein synthesis as well as some small-molecule metabolism processes. CircRNAs are relatively more conserved in closely related dermatophytes but rarely conserved in distantly related species. Tru_circ07138_001 is a highly conserved circRNA that was conserved in all ten dermatophytes analyzed in our study and three distantly related species. Its host gene TERG_07138 was also highly conserved in two of these distantly related species Gallus gallus and Caenorhabditis elegans. The specific role of this circRNA deserves further exploration. CONCLUSIONS: Our study is the first to provide a global profile of circRNAs in T. rubrum as well as dermatophytes. These results could serve as valuable resources for research on circRNA regulatory mechanisms in fungi and reveal new insights for further investigation of the physical characteristics of these significant human fungal pathogens.

Proteome-Wide Identification of Lysine Propionylation in the Conidial and Mycelial Stages of Trichophyton rubrum.

Posttranslational modifications (PTMs) exist in a wide variety of organisms and play key roles in regulating various essential biological processes. Lysine propionylation is a newly discovered PTM that has rarely been identified in fungi. Trichophyton rubrum (T. rubrum) is one of the most common fungal pathogens in the world and has been studied as an important model organism of anthropic pathogenic filamentous fungi. In this study, we performed a proteome-wide propionylation analysis in the conidial and mycelial stages of T. rubrum. A total of 157 propionylated sites on 115 proteins were identified, and the high confidence of propionylation identification was validated by parallel reaction monitoring (PRM) assay. The results show that the propionylated proteins were mostly involved in various metabolic pathways. Histones and 15 pathogenicity-related proteins were also targets for propionylation modification, suggesting their roles in epigenetic regulation and pathogenicity. A comparison of the conidial and mycelial stages revealed that most propionylated proteins and sites were growth-stage specific and independent of protein abundance. Based on the function classifications, the propionylated proteins had a similar distribution in both stages; however, some differences were also identified. Furthermore, our results show that the concentration of propionyl-CoA had a significant influence on the propionylation level. In addition to the acetylation, succinylation and propionylation identified in T. rubrum, 26 other PTMs were also found to exist in this fungus. Overall, our study provides the first global propionylation profile of a pathogenic fungus. These results would be a foundation for further research on the regulation mechanism of propionylation in T. rubrum, which will enhance our understanding of the physiological features of T. rubrum and provide some clues for the exploration of improved therapies to treat this medically important fungus.

Integrated microRNA and mRNA analysis in the pathogenic filamentous fungus Trichophyton rubrum.

BACKGROUND: Trichophyton rubrum (T. rubrum) is an important model organism of dermatophytes, which are the most common fungal pathogens worldwide. Despite the severity and prevalence of the infection caused by these pathogens, current therapies are not sufficient. MicroRNA (miRNA) is a class of small noncoding RNAs that are key factors in the regulation of gene expression. These miRNAs are reported to be highly conserved in different organisms and are involved in various essential cellular processes. In this study, we performed an integrated analysis of microRNA-like RNAs (milRNAs) and mRNAs between conidial and mycelial stages to investigate the roles of milRNAs in regulating the expression of target genes in T. rubrum. RESULTS: A total of 158 conserved milRNAs and 12 novel milRNAs were identified in our study, corresponding to 5470 target genes, which were involved in various essential biological pathways. In addition, 137 target genes corresponding to 21 milRNAs were concurrent differentially expressed between the conidial and mycelial stages. Among these 137 target genes, 64 genes showed the opposite trend to their corresponding milRNAs in expression difference between the two stages, indicating possible negative regulation. Furthermore, 46% of differentially expressed target genes are involved in transcription, transcriptional and post-transcriptional regulation. Our results indicate that milRNAs might associate with other regulatory elements to control gene expression at both transcriptional and post-transcriptional level. CONCLUSIONS: This study provides the first analysis of milRNA expression profile in T. rubrum as well as dermatophytes in general. The results revealed the roles of milRNAs in regulating gene expression between the two major growth stages of this fungus. Our study deepens our understanding of T. rubrum and will serve as a foundation for further investigations to combat this fungus.

The First Whole-Cell Proteome- and Lysine-Acetylome-Based Comparison between Trichophyton rubrum Conidial and Mycelial Stages.

Trichophyton rubrum is the most common fungal pathogen in the world, which has been studied as an important dermatophyte model organism. Despite the prevalence of T. rubrum, the available antifungal therapies are not sufficiently efficient. In this study, we performed the first comparison between the two major growth stages of T. rubrum: conidial and mycelial stages, based on their whole-cell proteomes and lysine acetylomes. In total, 4343 proteins were identified in both stages, and 1879 proteins were identified as differentially expressed between the two stages. The results showed that secretory proteases were more abundant in conidia, while aerobic metabolism and protein synthesis were significantly activated in the mycelial stage. In addition, 386 acetylated sites on 285 proteins and 5414 acetylated sites on 2335 proteins were identified in conidia and mycelia, respectively. The acetylation modifications were highly involved in metabolism and protein synthesis in both stages but differentially involved in Kyoto Encyclopedia of Genes and Genomes pathways and in epigenetic regulation between the two stages. Furthermore, inhibition of acetyltransferases or deacetylases significantly inhibited fungal growth and induced apoptosis. These results will enhance our understanding of the biological and physiological characteristics of T. rubrum and facilitate the development of improved therapies targeting these medically important pathogenic fungi.

The first succinylome profile of Trichophyton rubrum reveals lysine succinylation on proteins involved in various key cellular processes.

BACKGROUND: Dermatophytes, the most common cause of fungal infections, affect millions of individuals worldwide. They pose a major threat to public health because of the severity and longevity of infections caused by dermatophytes and their refractivity to therapy. Trichophyton rubrum (T. rubrum), the most common dermatophyte species, is a promising model organism for dermatophyte research. Post-translational modifications (PTMs) have been shown to be essential for many biological processes, particularly in the regulation of key cellular processes that contribute to pathogenicity. Although PTMs have important roles, little is known about their roles in T. rubrum and other dermatophytes. Succinylation is a new PTM that has recently been identified. In this study, we assessed the proteome-wide succinylation profile of T. rubrum. This study sought to systematically identify the succinylated sites and proteins in T. rubrum and to reveal the roles of succinylated proteins in various cellular processes as well as the differences in the succinylation profiles in different growth stages of the T. rubrum life cycle. RESULTS: A total of 569 succinylated lysine sites were identified in 284 proteins. These succinylated proteins are involved in various cellular processes, such as metabolism, translation and epigenetic regulation. Additionally, 24 proteins related to pathogenicity were found to be succinylated. Comparison of the succinylome at the conidia and mycelia stages revealed that most of the succinylated proteins and sites were growth-stage specific. In addition, the succinylation modifications on histone and ribosomal proteins were significantly different between these two growth stages. Moreover, the sequence features surrounding the succinylated sites were different in the two stages, thus indicating the specific recognition of succinyltransferases in each growth phase. CONCLUSIONS: In this study, we explored the first T. rubrum succinylome, which is also the first PTM analysis of dermatophytes reported to date. These results revealed the major roles of the succinylated proteins involved in T. rubrum and the differences in the succinylomes between the two major growth stages. These findings should improve understanding of the physiological and pathogenic properties of dermatophytes and facilitate future development of novel drugs and therapeutics for treating superficial fungal infections.

Proteogenomic Analysis of Trichophyton rubrum Aided by RNA Sequencing.

Infections caused by dermatophytes, Trichophyton rubrum in particular, are among the most common diseases in humans. In this study, we present a proteogenomic analysis of T. rubrum based on whole-genome proteomics and RNA-Seq studies. We confirmed 4291 expressed proteins in T. rubrum and validated their annotated gene structures based on 35 874 supporting peptides. In addition, we identified 323 novel peptides (not present in the current annotated protein database of T. rubrum) that can be used to enhance current T. rubrum annotations. A total of 104 predicted genes supported by novel peptides were identified, and 127 gene models suggested by the novel peptides that conflicted with existing annotations were manually assigned based on transcriptomic evidence. RNA-Seq confirmed the validity of 95% of the total peptides. Our study provides evidence that confirms and improves the genome annotation of T. rubrum and represents the first survey of T. rubrum genome annotations based on experimental evidence. Additionally, our integrated proteomics and multisourced transcriptomics approach provides stronger evidence for annotation refinement than proteomic data alone, which helps to address the dilemma of one-hit wonders (uncertainties supported by only one peptide).

Analysis of gene expression changes in Trichophyton rubrum after skin interaction.

Trichophyton rubrum, an anthropophilic and cosmopolitan fungus, is the most common agent of superficial mycoses. In this study, T. rubrum infection was modelled by adding human skin sections to a limited medium containing glucose and cDNA microarrays were used to monitor T. rubrum gene expression patterns on a global level. We observed that exposure to human skin resulted in upregulation of the expression levels of T. rubrum genes related to many cellular and biological processes, including transcription and translation, metabolism and secondary transport, the stress response, and signalling pathways. These results provide a reference set of T. rubrum genes whose expression patterns change upon infection and reveal previously unknown genes that most likely correspond to proteins that should be considered as virulence factor candidates and potential new drug targets for T. rubrum infection.

Analysis of the secretome and identification of novel constituents from culture filtrate of bacillus Calmette-Guerin using high-resolution mass spectrometry.

Tuberculosis (TB) is an infectious bacterial disease that causes morbidity and mortality, especially in developing countries. Although its efficacy against TB has displayed a high degree of variability (0%-80%) in different trials, Mycobacterium bovis bacillus Calmette-Guérin (BCG) has been recognized as an important weapon for preventing TB worldwide for over 80 years. Because secreted proteins often play vital roles in the interaction between bacteria and host cells, the secretome of mycobacteria is considered to be an attractive reservoir of potential candidate antigens for the development of novel vaccines and diagnostic reagents. In this study, we performed a proteomic analysis of BCG culture filtrate proteins using SDS-PAGE and high-resolution Fourier transform mass spectrometry. In total, 239 proteins (1555 unique peptides) were identified, including 185 secreted proteins or lipoproteins. Furthermore, 17 novel protein products not annotated in the BCG database were detected and validated by means of RT-PCR at the transcriptional level. Additionally, the translational start sites of 52 proteins were confirmed, and 22 proteins were validated through extension of the translational start sites based on N-terminus-derived peptides. There are 103 secreted proteins that have not been reported in previous studies on BCG [corrected] secretome and are unique to our study. The physicochemical characteristics of the secreted proteins were determined. Major components from the culture supernatant, including low-molecular-weight antigens, lipoproteins, Pro-Glu and Pro-Pro-Glu family proteins, and Mce family proteins, are discussed; some components represent potential predominant antigens in the humoral and cellular immune responses.

Identification and characterisation of non-coding small RNAs in the pathogenic filamentous fungus Trichophyton rubrum.

BACKGROUND: Accumulating evidence demonstrates that non-coding RNAs (ncRNAs) are indispensable components of many organisms and play important roles in cellular events, regulation, and development. RESULTS: Here, we analysed the small non-coding RNA (ncRNA) transcriptome of Trichophyton rubrum by constructing and sequencing a cDNA library from conidia and mycelia. We identified 352 ncRNAs and their corresponding genomic loci. These ncRNA candidates included 198 entirely novel ncRNAs and 154 known ncRNAs classified as snRNAs, snoRNAs and other known ncRNAs. Further bioinformatic analysis detected 96 snoRNAs, including 56 snoRNAs that had been annotated in other organisms and 40 novel snoRNAs. All snoRNAs belonged to two major classes--C/D box snoRNAs and H/ACA snoRNAs--and their potential target sites in rRNAs and snRNAs were predicted. To analyse the evolutionary conservation of the ncRNAs in T. rubrum, we aligned all 352 ncRNAs to the genomes of six dermatophytes and to the NCBI non-redundant nucleotide database (NT). The results showed that most of the identified snRNAs were conserved in dermatophytes. Of the 352 ncRNAs, 102 also had genomic loci in other dermatophytes, and 27 were dermatophyte-specific. CONCLUSIONS: Our systematic analysis may provide important clues to the function and evolution of ncRNAs in T. rubrum. These results also provide important information to complement the current annotation of the T. rubrum genome, which primarily comprises protein-coding genes.

Global gene expression profiles for the growth phases of Trichophyton rubrum.

Trichophyton rubrum (T. rubrum) is a common superficial fungus. Molecular and genetic studies of T. rubrum are still limited. In this paper, we report the global analysis of gene expression profiles at different growth phases using cDNA microarray technology. A total of 2044 differentially expressed genes were obtained and clustered into three expression patterns. Our data confirmed previous results that many mRNAs were pre-stored in the conidia of T. rubrum. Transcriptional profiling and function analysis showed that some glycolytic enzymes share similar expression patterns and may be coregulated during the transition of growth phases. Some genes involved in small GTPase signaling pathways, and in cAMP-dependent and MAPK regulation pathways were induced in response to the growth dynamics of T. rubrum. Although the detailed biological roles of these T. rubrum genes are still unknown, our results suggest that these genes may be involved in regulation mechanisms in the life cycle of the fungus.

Complete genome sequence of the extremophilic Bacillus cereus strain Q1 with industrial applications.

Bacillus cereus strain Q1 was isolated from a deep-subsurface oil reservoir in the Daqing oil field in northeastern China. This strain is able to produce biosurfactants and to survive in extreme environments. Here we report the finished and annotated genome sequence of this organism.

Genotypic characterization of Neisseria meningitidis serogroup B strains circulating in China.

OBJECTIVE: In China, comparatively little research has been directed at serogroup B meningococci, which are mainly isolated from healthy individuals. We attempted to study the genotypic characterization of Neisseria meningitidis serogroup B strains. METHODS: We analyzed 150 N. meningitidis strains isolated in China during 1975-2005 by multilocus sequence typing (MLST) and porA typing. RESULTS: A total of 88 different sequence types (STs) were identified by MLST, 73 of which were newly identified. Seven complexes previously identified in other countries and three unique clonal lineages first identified in China were detected, seven of which had previously been described as 'hyperinvasive meningococcal lineages'. Several lineages were found in specified period. A total of 63 different porA types were found, 11 of which were novel. The most common porA types were P1.5-1,2-2 (17 isolates), P1.5-1,10-4 (12 isolates), P1.5-2,2-2 (eight isolates) and P1.7-2,4 (seven isolates). CONCLUSION: In this context, serogroup B meningococci provide a diverse, continually reassorted gene pool from which new genotypes arise. The most important mechanism is probably horizontal genetic exchange among N. meningitidis serogroup B strains, possibly resulting in the emergence of new meningococcal clones. These results may help our understanding of the genotypic distribution of serogroup B meningococci and provide clues for further study of this organism.

Comparative analysis of whole genome structure of Streptococcus suis using whole genome PCR scanning.

An outbreak associated with Streptococcus suis infection in humans emerged in Sichuan province, China in 2005. The outbreak is atypical for the apparent large number of human cases, high fatality rate and geographical spread. To determine whether the bacterium has changed, we compared both human and animal isolates from the Sichuan outbreak with those collected previously within China and in other countries using whole genome PCR scanning (WGPScaning) comparative sequencing of several known virulence factor genes and multilocus sequence typing (MLST) analysis. WGPScanning analysis showed that all primer pairs yielded PCR products of the expected sizes in all four strains tested. The nucleotide sequences of all the detected virulence factor genes are identical in the four strains and MLST results showed that the four isolates studied and reference strain all belonged to the ST1 complex. No new genetic changes were found in the genome structure of the isolates from this Sichuan outbreak.

Characterization of ST-4821 complex, a unique Neisseria meningitidis clone.

Ten outbreaks of a new serogroup C meningococcal disease emerged during 2003-2005 in China. The multilocus sequence typing results indicated that unique sequence type 4821 clone meningococci were responsible for these outbreaks. Herein, we determined the entire genomic DNA sequence of serogroup C isolate 053442, which belongs to ST-4821. Comparison of 053442 gene contents with other meningococcal genomes shows that they have similar characteristics, including thousands of repetitive elements and simple sequence repeats, numerous phase-variable genes, and similar virulence-related factors. However, many strain-specific regions were found in each genome. We also present the results of a genomic comparison of 28 ST-4821 complex isolates that were isolated from different serogroups using comparative genomic hybridization analysis. Genome comparison between the newly emerged hyperinvasive isolates belonging to different serogroups will further our understanding of their respective pathogenetic mechanisms.

Molecular characterization of serogroup C Neisseria meningitidis isolated in China.

An increase in the number of serogroup C meningococcal disease cases occurred in China from September 2003 to January 2006 as a result of several successive outbreaks. In addition, the proportion of serogroup C Neisseria meningitidis isolates from sporadic cases and carriers has also increased. In this study, 113 serogroup C meningococcal isolates were characterized by multilocus sequence typing (MLST) and PorA typing. These isolates comprised those from outbreak cases and their close contacts, the national carriage survey conducted during the same period and some historical isolates from 1966-2002. Twenty MLST sequence types (STs) and 21 PorA variable region (VR) types were identified in the collection. The ST-4821 complex, a newly identified lineage, was the most prevalent lineage (95/113). These data also showed a high level of diversification of serogroup C isolates, as indicated by the number of variants of the ST-4821 clone and the VR types present. There were ten PorA VR types among the ST-4821 isolates, and certain VR types (P1.7-2,14, P1.12-1,16-8) were associated with isolates from outbreak cases. The results of this study allow us to draw a profile of the molecular characteristics of serogroup C strains in China. These data are helpful for monitoring the spread of virulent strains and will provide valuable information for the prevention of bacterial meningitis in China.

Genotypic analysis of serogroups other than A, B or C of Neisseria meningitidis in China.

To serologically and genetically characterize other serogroups (except A, B, and C) of Neisseria meningitidis isolates in China, we collected 56 strains of other serogroups, identified by serogroup typing and multilocus sequence typing (MLST). All of them are non-invasive isolates. The serogroups of the 56 Chinese isolates were W135 (11 isolates), Y (4), X (15), 29E (15), D (1), H (4), I (3), K (2), and non-groupable (1). By MLST, 34 different sequence types (STs) were identified, 28 of which were not found in the MLST database as of July 2006 and seemed to be unique to China. Statistical analysis of the MLST results revealed that, although the Chinese isolates seemed to be genetically divergent, they could be classified into 5 major clonal groups and other minor groups. Among these isolates, none of the well-documented ST complexes found worldwide was present.

The use of global transcriptional analysis to reveal the biological and cellular events involved in distinct development phases of Trichophyton rubrum conidial germination.

BACKGROUND: Conidia are considered to be the primary cause of infections by Trichophyton rubrum. RESULTS: We have developed a cDNA microarray containing 10250 ESTs to monitor the transcriptional strategy of conidial germination. A total of 1561 genes that had their expression levels specially altered in the process were obtained and hierarchically clustered with respect to their expression profiles. By functional analysis, we provided a global view of an important biological system related to conidial germination, including characterization of the pattern of gene expression at sequential developmental phases, and changes of gene expression profiles corresponding to morphological transitions. We matched the EST sequences to GO terms in the Saccharomyces Genome Database (SGD). A number of homologues of Saccharomyces cerevisiae genes related to signalling pathways and some important cellular processes were found to be involved in T. rubrum germination. These genes and signalling pathways may play roles in distinct steps, such as activating conidial germination, maintenance of isotropic growth, establishment of cell polarity and morphological transitions. CONCLUSION: Our results may provide insights into molecular mechanisms of conidial germination at the cell level, and may enhance our understanding of regulation of gene expression related to the morphological construction of T. rubrum.