Cell Surface最新文献

{"title":"Mycobacterium tuberculosis modifies cell wall carbohydrates during biofilm growth with a concomitant reduction in complement activation","authors":"Thomas Keating ,&nbsp;Samuel Lethbridge ,&nbsp;Jon C. Allnutt ,&nbsp;Charlotte L. Hendon-Dunn ,&nbsp;Stephen R. Thomas ,&nbsp;Luke J. Alderwick ,&nbsp;Stephen C. Taylor ,&nbsp;Joanna Bacon","doi":"10.1016/j.tcsw.2021.100065","DOIUrl":"10.1016/j.tcsw.2021.100065","url":null,"abstract":"<div><p>The development of new vaccines for TB needs to be underpinned by an understanding of both the molecular and cellular mechanisms of host-pathogen interactions and how the immune response can be modulated to achieve protection from disease. Complement orchestrates many aspects of the innate and adaptive immune responses. However, little is known about the contribution of the complement pathways during TB disease, particularly with respect to mycobacterial phenotype. Extracellular communities (biofilms) of <em>M. tuberculosis</em> are found in the acellular rim of granulomas, during disease, and these are likely to be present in post-primary TB episodes, in necrotic lesions. Our study aimed to determine which mycobacterial cell wall components were altered during biofilm growth and how these cell wall alterations modified the complement response. We have shown that <em>M. tuberculosis</em> biofilms modified their cell wall carbohydrates and elicited reduced classical and lectin pathway activation. Consistent with this finding was the reduction of C3b/iC3b deposition on biofilm cell wall carbohydrate extracts. Here, we have highlighted the role of cell wall carbohydrate alterations during biofilm growth of <em>M. tuberculosis</em> and subsequent modulation of complement activation.</p></div>","PeriodicalId":36539,"journal":{"name":"Cell Surface","volume":"7 ","pages":"Article 100065"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3a/4a/main.PMC8577165.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39891713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A small molecule inhibits cell elongation by modulating cell wall polysaccharide composition in Arabidopsis","authors":"Wenbo Li ,&nbsp;Qian Zhang ,&nbsp;Shumin Cao ,&nbsp;Laifu Luo ,&nbsp;Lingting Li ,&nbsp;Lili Gu ,&nbsp;Yang Zhao ,&nbsp;Laigeng Li","doi":"10.1016/j.tcsw.2021.100049","DOIUrl":"10.1016/j.tcsw.2021.100049","url":null,"abstract":"<div><p>The plant primary cell wall is comprised of pectin, cellulose and hemicelluloses, whose dynamic interactions play essential roles in plant cell elongation. Through a chemical genetics screening, we identified a small molecule, named cell wall modulator (CWM), which disrupted cell growth and deformed cell shape in etiolated <em>Arabidopsis</em> hypocotyl. A pectin defective mutant <em>qua2</em>, identified from screening an <em>Arabidopsis</em> EMS mutant library, showed a reduced sensitivity to CWM treatment. On the other hand, pectinase treatment suppressed the CWM induced phenotype. Furthermore, cellulose content was decreased in response to CWM treatment, while the cellulose synthesis mutants <em>ixr1</em> and <em>ixr2</em> were hypersensitive to CWM. Together, the study identified a small molecule CWM that induced a modification of the cell wall in elongating cells, likely through interfering with pectin modification. This molecule may be used as a tool to study cell wall remodeling during plant growth.</p></div>","PeriodicalId":36539,"journal":{"name":"Cell Surface","volume":"7 ","pages":"Article 100049"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.tcsw.2021.100049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25432416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure-function analysis of MmpL7-mediated lipid transport in mycobacteria","authors":"Nabiela Moolla ,&nbsp;Rebeca Bailo ,&nbsp;Robert Marshall ,&nbsp;Vassiliy N. Bavro ,&nbsp;Apoorva Bhatt","doi":"10.1016/j.tcsw.2021.100062","DOIUrl":"10.1016/j.tcsw.2021.100062","url":null,"abstract":"<div><p>Mycobacterial membrane protein Large (MmpL7) is a Resistance-Nodulation-Division (RND) family transporter required for the export of the virulence lipid, phthiocerol dimycocerosate (PDIM), in <em>Mycobacterium tuberculosis</em>. Using a null mutant of the related, vaccine strain <em>Mycobacterium bovis</em> BCG, we show that MmpL7 is also involved in the transport of the structurally related phenolic glycolipid (PGL), which is also produced by the hypervirulent <em>M. tuberculosis</em> strain HN878, but absent in <em>M. tuberculosis</em> H37Rv. Furthermore, we generated an <em>in silico</em> model of <em>M. tuberculosis</em> MmpL7 that revealed MmpL7 as a functional outlier within the MmpL-family, missing a canonical proton-relay signature sequence, suggesting that it employs a yet-unidentified mechanism for energy coupling for transport. In addition, our analysis demonstrates that the periplasmic porter domain 2 insert (PD2-insert), which doesn't share any recognisable homology, is highly alpha-helical in nature, suggesting an organisation similar to that seen in the hopanoid PD3/4 domains. Using the <em>M. bovis</em> BCG <em>mmpL7</em> mutant for functional complementation with mutated alleles of <em>mmpL7</em>, we were able to identify residues present in the transmembrane domains TM4 and TM10, and the PD2 domain insert that play a crucial role in PDIM transport, and in certain cases, biosynthesis of PDIM.</p></div>","PeriodicalId":36539,"journal":{"name":"Cell Surface","volume":"7 ","pages":"Article 100062"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.tcsw.2021.100062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39419194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucan and glycogen exist as a covalently linked macromolecular complex in the cell wall of Candida albicans and other Candida species","authors":"Douglas W. Lowman ,&nbsp;M. Sameer Al-Abdul-Wahid ,&nbsp;Zuchao Ma ,&nbsp;Michael D. Kruppa ,&nbsp;Elena Rustchenko ,&nbsp;David L. Williams","doi":"10.1016/j.tcsw.2021.100061","DOIUrl":"10.1016/j.tcsw.2021.100061","url":null,"abstract":"<div><p>The fungal cell wall serves as the interface between the organism and its environment. Complex carbohydrates are a major component of the <em>Candida albicans</em> cell wall, <em>i.e.</em>, glucan, mannan and chitin. β-Glucan is a pathogen associated molecular pattern (PAMP) composed of β-(1 → 3,1 → 6)-linked glucopyranosyl repeat units. This PAMP plays a key role in fungal structural integrity and immune recognition. Glycogen is an α-(1 → 4,1 → 6)-linked glucan that is an intracellular energy storage carbohydrate. We observed that glycogen was co-extracted during the isolation of β-glucan from <em>C. albicans</em> SC5314. We hypothesized that glucan and glycogen may form a macromolecular species that links intracellular glycogen with cell wall β-(1 → 3,1 → 6)-glucan. To test this hypothesis, we examined glucan-glycogen extracts by multi-dimensional NMR to ascertain if glycogen and β-glucan were interconnected. ¹H NMR analyses confirmed the presence of glycogen and β-glucan in the macromolecule. Diffusion Ordered SpectroscopY (DOSY) confirmed that the β-glucan and glycogen co-diffuse, which indicates a linkage between the two polymers. We determined that the linkage is not via peptides and/or small proteins. Our data indicate that glycogen is covalently linked to β-(1 → 3,1 → 6) glucan via the β -(1 → 6)-linked side chain. We also found that the glucan-glycogen complex was present in <em>C. dublinensis</em>, <em>C. haemulonii</em> and <em>C. auris</em>, but was not present in <em>C. glabrata</em> or <em>C. albicans</em> hyphal glucan. These data demonstrate that glucan and glycogen form a novel macromolecular complex in the cell wall of <em>C. albicans</em> and other <em>Candida</em> species<em>.</em> This new and unique structure expands our understanding of the cell wall in <em>Candida</em> species.</p></div>","PeriodicalId":36539,"journal":{"name":"Cell Surface","volume":"7 ","pages":"Article 100061"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.tcsw.2021.100061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39881168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elimination of PknL and MSMEG_4242 in Mycobacterium smegmatis alters the character of the outer cell envelope and selects for mutations in Lsr2","authors":"Estalina Báez-Ramírez ,&nbsp;Luis Querales ,&nbsp;Carlos Andres Aranaga ,&nbsp;Gustavo López ,&nbsp;Elba Guerrero ,&nbsp;Laurent Kremer ,&nbsp;Séverine Carrère-Kremer ,&nbsp;Albertus Viljoen ,&nbsp;Mamadou Daffé ,&nbsp;Françoise Laval ,&nbsp;Stewart T. Cole ,&nbsp;Andrej Benjak ,&nbsp;Pedro Alzari ,&nbsp;Gwenaëlle André-Leroux ,&nbsp;William R. Jacobs Jr. ,&nbsp;Catherine Vilcheze ,&nbsp;Howard E. Takiff","doi":"10.1016/j.tcsw.2021.100060","DOIUrl":"10.1016/j.tcsw.2021.100060","url":null,"abstract":"<div><p>Four serine/threonine kinases are present in all mycobacteria: PknA, PknB, PknG and PknL. PknA and PknB are essential for growth and replication, PknG regulates metabolism, but little is known about PknL. Inactivation of <em>pknL</em> and adjacent regulator <em>MSMEG_424</em>2 in rough colony <em>M. smegmatis</em> mc²155 produced both smooth and rough colonies. Upon restreaking rough colonies, smooth colonies appeared at a frequency of ~ 1/250. Smooth mutants did not form biofilms, showed increased sliding motility and anomalous lipids on thin-layer chromatography, identified by mass spectrometry as lipooligosaccharides and perhaps also glycopeptidolipids. RNA-seq and Sanger sequencing revealed that all smooth mutants had inactivated <em>lsr2</em> genes due to mutations and different IS<em>1096</em> insertions. When complemented with <em>lsr2</em>, the colonies became rough, anomalous lipids disappeared and sliding motility decreased. Smooth mutants showed increased expression of IS<em>1096</em> transposase TnpA and <em>MSMEG_4727</em>, which encodes a protein similar to PKS5. When <em>MSMEG_4727</em> was deleted, smooth <em>pknL/MSMEG_4242/lsr2</em> mutants reverted to rough, formed good biofilms, their motility decreased slightly and their anomalous lipids disappeared. Rough del<em>pknL/del4242</em> mutants formed poor biofilms and showed decreased, aberrant sliding motility and both phenotypes were complemented with the two deleted genes. Inactivation of <em>lsr2</em> changes colony morphology from rough to smooth, augments sliding motility and increases expression of <em>MSMEG_4727</em> and other enzymes synthesizing lipooligosaccharides, apparently preventing biofilm formation. Similar morphological phase changes occur in other mycobacteria, likely reflecting environmental adaptations. PknL and <em>MSMEG_4242</em> regulate lipid components of the outer cell envelope and their absence selects for <em>lsr2</em> inactivation<em>.</em> A regulatory, phosphorylation cascade model is proposed.</p></div>","PeriodicalId":36539,"journal":{"name":"Cell Surface","volume":"7 ","pages":"Article 100060"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.tcsw.2021.100060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10224261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disruption of protein rhamnosylation affects the Sporothrix schenckii-host interaction","authors":"Alma K. Tamez-Castrellón ,&nbsp;Samantha L. van der Beek ,&nbsp;Luz A. López-Ramírez ,&nbsp;Iván Martínez-Duncker ,&nbsp;Nancy E. Lozoya-Pérez ,&nbsp;Nina M. van Sorge ,&nbsp;Héctor M. Mora-Montes","doi":"10.1016/j.tcsw.2021.100058","DOIUrl":"10.1016/j.tcsw.2021.100058","url":null,"abstract":"<div><p>Sporotrichosis is a fungal disease caused by the members of the <em>Sporothrix</em> pathogenic clade, and one of the etiological agents is <em>Sporothrix schenckii.</em> The cell wall of this organism has been previously analyzed and thus far is known to contain an inner layer composed of chitin and β -glucans, and an outer layer of glycoproteins, which are decorated with mannose and rhamnose-containing oligosaccharides. The L-rhamnose biosynthesis pathway is common in bacteria but rare in members of the Fungi kingdom. Therefore, in this study, we aimed to disrupt this metabolic route to assess the contribution of rhamnose during the <em>S.<!--> <!-->schenckii</em>-host interaction. We identified and silenced in <em>S. schenckii</em> a functional ortholog of the bacterial <em>rmlD</em> gene, which encodes for an essential reductase for the synthesis of nucleotide-activated L-rhamnose. <em>RmlD</em> silencing did not affect fungal growth or morphology but decreased cell wall rhamnose content. Compensatory, the β-1,3-glucan levels increased and were more exposed at the cell surface. Moreover, when incubated with human peripheral blood mononuclear cells, the <em>RmlD</em> silenced mutants differentially stimulated cytokine production when compared with the wild-type strain, reducing TNFα and IL-6 levels and increasing IL-1 β and IL-10 production. Upon incubation with human monocyte-derived macrophages, the silenced strains were more efficiently phagocytosed than the wild-type strain. In both cases, our data suggest that rhamnose-based oligosaccharides are ligands that interact with TLR4. Finally, our findings showed that cell wall rhamnose is required for the <em>S. schenckii</em> virulence in the <em>G. mellonella</em> model of infection.</p></div>","PeriodicalId":36539,"journal":{"name":"Cell Surface","volume":"7 ","pages":"Article 100058"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.tcsw.2021.100058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39221430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cryptococcus neoformans Cda1 and Cda2 coordinate deacetylation of chitin during infection to control fungal virulence","authors":"Rajendra Upadhya ,&nbsp;Woei C. Lam ,&nbsp;Camaron R. Hole ,&nbsp;Danealle Parchment ,&nbsp;Chrono K. Lee ,&nbsp;Charles A. Specht ,&nbsp;Stuart M. Levitz ,&nbsp;Jennifer K. Lodge","doi":"10.1016/j.tcsw.2021.100066","DOIUrl":"10.1016/j.tcsw.2021.100066","url":null,"abstract":"<div><p>Chitosan, a deacetylated form of chitin, is required for the virulence of <em>Cryptococcus neoformans</em>. There are three chitin deacetylase genes (CDA) that are essential for chitosan production, and deletion of all three genes results in the absence of chitosan, loss of virulence, and induction of a protective host response when used as a vaccine. Cda1 plays a major role in deacetylating chitin during pulmonary infection of CBA/J mice. Inoculation with the <em>cda</em>1Δ strain did not lead to a lethal infection. However, the infection was not cleared. The persistence of the fungus in the host suggests that chitin is still being deacetylated by Cda2 and/or Cda3. To test this hypothesis, we subjected strains deleted of two CDA genes to fungal virulence in CBA/J, C57BL/6 and BALB/c and found that <em>cda</em>1Δ<em>cda</em>2Δ was avirulent in all mouse lines, as evidenced by its complete clearance. Consistent with the major role of Cda1 in CBA/J, we found that <em>cda</em>2Δ<em>cda</em>3Δ was as virulent as its wild-type progenitor KN99. On the other hand, <em>cda</em>1Δ<em>cda</em>3Δ displayed virulence comparable to that of <em>cda</em>1Δ. The virulence of each mutant correlates with the amount of chitosan produced when grown under host-mimicking culture conditions. In addition, the avirulence of <em>cda</em>1Δ<em>cda</em>2Δ was followed by the induction of a protective immune response in C57BL/6 and CBA/J mice, when a live or heat-killed form of the mutant was used as a vaccine respectively. Taken together, these data imply that, in <em>C. neoformans</em>, coordinated activity of both Cda1 and Cda2 is essential for mediating fungal virulence.</p></div>","PeriodicalId":36539,"journal":{"name":"Cell Surface","volume":"7 ","pages":"Article 100066"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cb/85/main.PMC8529172.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39572361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lytic transglycosylase MltG cleaves in nascent peptidoglycan and produces short glycan strands","authors":"Jad Sassine ,&nbsp;Manuel Pazos ,&nbsp;Eefjan Breukink ,&nbsp;Waldemar Vollmer","doi":"10.1016/j.tcsw.2021.100053","DOIUrl":"10.1016/j.tcsw.2021.100053","url":null,"abstract":"<div><p>Bacteria encase their cytoplasmic membrane with peptidoglycan (PG) to maintain the shape of the cell and protect it from bursting. The enlargement of the PG layer is facilitated by the coordinated activities of PG synthesising and -cleaving enzymes. In <em>Escherichia coli</em>, the cytoplasmic membrane-bound lytic transglycosylase MltG associates with PG synthases and was suggested to terminate the polymerisation of PG glycan strands. Using pull-down and surface plasmon resonance, we detected interactions between MltG from <em>Bacillus subtilis</em> and two PG synthases; the class A PBP1 and the class B PBP2B. Using <em>in vitro</em> PG synthesis assays with radio-labelled or fluorophore-labelled <em>B. subtilis</em>-type and/or <em>E. coli</em>-type lipid II, we showed that both, <em>Bs</em>MltG and <em>Ec</em>MltG, are lytic tranglycosylases and that their activity is higher during ongoing glycan strand polymerisation. MltG competed with the transpeptidase activity of class A PBPs, but had no effect on their glycosyltransferase activity, and produced glycan strands with a length of 7 disaccharide units from cleavage in the nascent strands. We hypothesize that MltG cleaves the nascent strands to produce short glycan strands that are used in the cell for a yet unknown process.</p></div>","PeriodicalId":36539,"journal":{"name":"Cell Surface","volume":"7 ","pages":"Article 100053"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.tcsw.2021.100053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38949676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The divergent roles of sortase in the biology of Gram-positive bacteria","authors":"Aliyath Susmitha ,&nbsp;Harsha Bajaj ,&nbsp;Kesavan Madhavan Nampoothiri","doi":"10.1016/j.tcsw.2021.100055","DOIUrl":"10.1016/j.tcsw.2021.100055","url":null,"abstract":"<div><p>The bacterial cell wall contains numerous surface-exposed proteins, which are covalently anchored and assembled by a sortase family of transpeptidase enzymes. The sortase are cysteine transpeptidases that catalyzes the covalent attachment of surface protein to the cell wall peptidoglycan. Among the reported six classes of sortases, each distinct class of sortase plays a unique biological role in anchoring a variety of surface proteins to the peptidoglycan of both pathogenic and non-pathogenic Gram-positive bacteria. Sortases not only exhibit virulence and pathogenesis properties to host cells, but also possess a significant role in gut retention and immunomodulation in probiotic microbes. The two main distinct functions are to attach proteins directly to the cell wall or assemble pili on the microbial surface. This review provides a compendium of the distribution of different classes of sortases present in both pathogenic and non-pathogenic Gram-positive bacteria and also the noteworthy role played by them in bacterial cell wall assembly which enables each microbe to effectively interact with its environment.</p></div>","PeriodicalId":36539,"journal":{"name":"Cell Surface","volume":"7 ","pages":"Article 100055"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.tcsw.2021.100055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39124404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mycobacterium abscessus biofilms produce an extracellular matrix and have a distinct mycolic acid profile","authors":"Anja Dokic ,&nbsp;Eliza Peterson ,&nbsp;Mario L. Arrieta-Ortiz ,&nbsp;Min Pan ,&nbsp;Alessandro Di Maio ,&nbsp;Nitin Baliga ,&nbsp;Apoorva Bhatt","doi":"10.1016/j.tcsw.2021.100051","DOIUrl":"10.1016/j.tcsw.2021.100051","url":null,"abstract":"<div><p>A non-tuberculous mycobacterium, <em>Mycobacterium abscessus</em> is an emerging opportunistic pathogen associated with difficult to treat pulmonary infections, particularly in patients suffering from cystic fibrosis. It is capable of forming biofilms <em>in vitro</em> that result in an increase of already high levels of antibiotic resistance in this bacterium. Evidence that <em>M. abscessus</em> forms biofilm-like microcolonies in patient lungs and on medical devices further implicated the need to investigate this biofilm in detail. Therefore, in this study we characterized the <em>M. abscessus</em> pellicular biofilm, formed on a liquid–air interface, by studying its molecular composition, and its transcriptional profile in comparison to planktonic cells. Using scanning electron micrographs and fluorescence microscopy, we showed that <em>M. abscessus</em> biofilms produce an extracellular matrix composed of lipids, proteins, carbohydrates and extracellular DNA. Transcriptomic analysis of biofilms revealed an upregulation of pathways involved in the glyoxylate shunt, redox metabolism and mycolic acid biosynthesis. Genes involved in elongation and desaturation of mycolic acids were highly upregulated in biofilms and, mirroring those findings, biochemical analysis of mycolates revealed molecular changes and an increase in mycolic acid chain length. Together these results give us an insight into the complex structure of <em>M. abscessus</em> biofilms, the understanding of which may be adapted for clinical use in treatment of biofilm infections, including strategies for dispersing the extracellular matrix, allowing antibiotics to gain access to bacteria within the biofilm.</p></div>","PeriodicalId":36539,"journal":{"name":"Cell Surface","volume":"7 ","pages":"Article 100051"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.tcsw.2021.100051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38919857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}