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Discovery and characterization of a Gram-positive Pel polysaccharide biosynthetic gene cluster.

Whitfield GB, Marmont LS, Bundalovic-Torma C, Razvi E, Roach EJ, Khursigara CM, Parkinson J, Howell PL.

PLoS Pathog. 2020 Apr 1;16(4):e1008281. doi: 10.1371/journal.ppat.1008281. eCollection 2020 Apr.


A systematic pipeline for classifying bacterial operons reveals the evolutionary landscape of biofilm machineries.

Bundalovic-Torma C, Whitfield GB, Marmont LS, Howell PL, Parkinson J.

PLoS Comput Biol. 2020 Apr 1;16(4):e1007721. doi: 10.1371/journal.pcbi.1007721. eCollection 2020 Apr.


Reducing Aspergillus fumigatus Virulence through Targeted Dysregulation of the Conidiation Pathway.

Stewart JIP, Fava VM, Kerkaert JD, Subramanian AS, Gravelat FN, Lehoux M, Howell PL, Cramer RA, Sheppard DC.

mBio. 2020 Feb 4;11(1). pii: e03202-19. doi: 10.1128/mBio.03202-19.


Pel Polysaccharide Biosynthesis Requires an Inner Membrane Complex Comprised of PelD, PelE, PelF, and PelG.

Whitfield GB, Marmont LS, Ostaszewski A, Rich JD, Whitney JC, Parsek MR, Harrison JJ, Howell PL.

J Bacteriol. 2020 Mar 26;202(8). pii: e00684-19. doi: 10.1128/JB.00684-19. Print 2020 Mar 26.


Multiple conformations facilitate PilT function in the type IV pilus.

McCallum M, Benlekbir S, Nguyen S, Tammam S, Rubinstein JL, Burrows LL, Howell PL.

Nat Commun. 2019 Nov 15;10(1):5198. doi: 10.1038/s41467-019-13070-z.


Synthesis of defined mono-de-N-acetylated β-(1→6)-N-acetyl-d-glucosamine oligosaccharides to characterize PgaB hydrolase activity.

Forman A, Pfoh R, Eddenden A, Howell PL, Nitz M.

Org Biomol Chem. 2019 Nov 6;17(43):9456-9466. doi: 10.1039/c9ob02079a.


Ega3 from the fungal pathogen Aspergillus fumigatus is an endo-α-1,4-galactosaminidase that disrupts microbial biofilms.

Bamford NC, Le Mauff F, Subramanian AS, Yip P, Millán C, Zhang Y, Zacharias C, Forman A, Nitz M, Codée JDC, Usón I, Sheppard DC, Howell PL.

J Biol Chem. 2019 Sep 13;294(37):13833-13849. doi: 10.1074/jbc.RA119.009910. Epub 2019 Aug 15.


Molecular mechanism of Aspergillus fumigatus biofilm disruption by fungal and bacterial glycoside hydrolases.

Le Mauff F, Bamford NC, Alnabelseya N, Zhang Y, Baker P, Robinson H, Codée JDC, Howell PL, Sheppard DC.

J Biol Chem. 2019 Jul 12;294(28):10760-10772. doi: 10.1074/jbc.RA119.008511. Epub 2019 Jun 5.


Treatment with the Pseudomonas aeruginosa Glycoside Hydrolase PslG Combats Wound Infection by Improving Antibiotic Efficacy and Host Innate Immune Activity.

Pestrak MJ, Baker P, Dellos-Nolan S, Hill PJ, Passos da Silva D, Silver H, Lacdao I, Raju D, Parsek MR, Wozniak DJ, Howell PL.

Antimicrob Agents Chemother. 2019 May 24;63(6). pii: e00234-19. doi: 10.1128/AAC.00234-19. Print 2019 Jun.


The Dynamic Structures of the Type IV Pilus.

McCallum M, Burrows LL, Howell PL.

Microbiol Spectr. 2019 Mar;7(2). doi: 10.1128/microbiolspec.PSIB-0006-2018. Review.


Galactosaminogalactan (GAG) and its multiple roles in Aspergillus pathogenesis.

Speth C, Rambach G, Lass-Flörl C, Howell PL, Sheppard DC.

Virulence. 2019 Dec;10(1):976-983. doi: 10.1080/21505594.2019.1568174. Epub 2019 Jan 22.


Deacetylated microbial biofilm exopolysaccharides: It pays to be positive.

Ostapska H, Howell PL, Sheppard DC.

PLoS Pathog. 2018 Dec 27;14(12):e1007411. doi: 10.1371/journal.ppat.1007411. eCollection 2018 Dec. Review. No abstract available.


Gram-negative synthase-dependent exopolysaccharide biosynthetic machines.

Low KE, Howell PL.

Curr Opin Struct Biol. 2018 Dec;53:32-44. doi: 10.1016/ Epub 2018 May 26. Review.


PgaB orthologues contain a glycoside hydrolase domain that cleaves deacetylated poly-β(1,6)-N-acetylglucosamine and can disrupt bacterial biofilms.

Little DJ, Pfoh R, Le Mauff F, Bamford NC, Notte C, Baker P, Guragain M, Robinson H, Pier GB, Nitz M, Deora R, Sheppard DC, Howell PL.

PLoS Pathog. 2018 Apr 23;14(4):e1006998. doi: 10.1371/journal.ppat.1006998. eCollection 2018 Apr.


Non-eluting, surface-bound enzymes disrupt surface attachment of bacteria by continuous biofilm polysaccharide degradation.

Asker D, Awad TS, Baker P, Howell PL, Hatton BD.

Biomaterials. 2018 Jun;167:168-176. doi: 10.1016/j.biomaterials.2018.03.016. Epub 2018 Mar 14.


Molecular Basis for the Attachment of S-Layer Proteins to the Cell Wall of Bacillus anthracis.

Sychantha D, Chapman RN, Bamford NC, Boons GJ, Howell PL, Clarke AJ.

Biochemistry. 2018 Apr 3;57(13):1949-1953. doi: 10.1021/acs.biochem.8b00060. Epub 2018 Mar 14.


Hoisted by their own petard: do microbial enzymes hold the solution to treating and preventing biofilm infections?

Snarr BD, Howell PL, Sheppard DC.

Future Microbiol. 2018 Mar;13:395-398. doi: 10.2217/fmb-2017-0243. Epub 2018 Feb 14. No abstract available.


Conserved, unstructured regions in Pseudomonas aeruginosa PilO are important for type IVa pilus function.

Leighton TL, Mok MC, Junop MS, Howell PL, Burrows LL.

Sci Rep. 2018 Feb 8;8(1):2600. doi: 10.1038/s41598-018-20925-w.


PatB1 is an O-acetyltransferase that decorates secondary cell wall polysaccharides.

Sychantha D, Little DJ, Chapman RN, Boons GJ, Robinson H, Howell PL, Clarke AJ.

Nat Chem Biol. 2018 Jan;14(1):79-85. doi: 10.1038/nchembio.2509. Epub 2017 Oct 30.


In vitro characterization of the antivirulence target of Gram-positive pathogens, peptidoglycan O-acetyltransferase A (OatA).

Sychantha D, Jones CS, Little DJ, Moynihan PJ, Robinson H, Galley NF, Roper DI, Dowson CG, Howell PL, Clarke AJ.

PLoS Pathog. 2017 Oct 27;13(10):e1006667. doi: 10.1371/journal.ppat.1006667. eCollection 2017 Oct.


PelA and PelB proteins form a modification and secretion complex essential for Pel polysaccharide-dependent biofilm formation in Pseudomonas aeruginosa.

Marmont LS, Whitfield GB, Rich JD, Yip P, Giesbrecht LB, Stremick CA, Whitney JC, Parsek MR, Harrison JJ, Howell PL.

J Biol Chem. 2017 Nov 24;292(47):19411-19422. doi: 10.1074/jbc.M117.812842. Epub 2017 Sep 27.


Chemical synthesis of guanosine diphosphate mannuronic acid (GDP-ManA) and its C-4-O-methyl and C-4-deoxy congeners.

Zhang Q, Howell PL, Overkleeft HS, Filippov DV, van der Marel GA, Codée JDC.

Carbohydr Res. 2017 Oct 10;450:12-18. doi: 10.1016/j.carres.2017.08.005. Epub 2017 Aug 11.


Microbial glycoside hydrolases as antibiofilm agents with cross-kingdom activity.

Snarr BD, Baker P, Bamford NC, Sato Y, Liu H, Lehoux M, Gravelat FN, Ostapska H, Baistrocchi SR, Cerone RP, Filler EE, Parsek MR, Filler SG, Howell PL, Sheppard DC.

Proc Natl Acad Sci U S A. 2017 Jul 3;114(27):7124-7129. doi: 10.1073/pnas.1702798114. Epub 2017 Jun 20.


Cyclic AMP-Independent Control of Twitching Motility in Pseudomonas aeruginosa.

Buensuceso RNC, Daniel-Ivad M, Kilmury SLN, Leighton TL, Harvey H, Howell PL, Burrows LL.

J Bacteriol. 2017 Jul 25;199(16). pii: e00188-17. doi: 10.1128/JB.00188-17. Print 2017 Aug 15.


The molecular mechanism of the type IVa pilus motors.

McCallum M, Tammam S, Khan A, Burrows LL, Howell PL.

Nat Commun. 2017 May 5;8:15091. doi: 10.1038/ncomms15091.


Pseudomonas aeruginosa Alginate Overproduction Promotes Coexistence with Staphylococcus aureus in a Model of Cystic Fibrosis Respiratory Infection.

Limoli DH, Whitfield GB, Kitao T, Ivey ML, Davis MR Jr, Grahl N, Hogan DA, Rahme LG, Howell PL, O'Toole GA, Goldberg JB.

mBio. 2017 Mar 21;8(2). pii: e00186-17. doi: 10.1128/mBio.00186-17.


Oligomeric lipoprotein PelC guides Pel polysaccharide export across the outer membrane of Pseudomonas aeruginosa.

Marmont LS, Rich JD, Whitney JC, Whitfield GB, Almblad H, Robinson H, Parsek MR, Harrison JJ, Howell PL.

Proc Natl Acad Sci U S A. 2017 Mar 14;114(11):2892-2897. doi: 10.1073/pnas.1613606114. Epub 2017 Feb 27.


The Type IVa Pilus Machinery Is Recruited to Sites of Future Cell Division.

Carter T, Buensuceso RN, Tammam S, Lamers RP, Harvey H, Howell PL, Burrows LL.

mBio. 2017 Jan 31;8(1). pii: e02103-16. doi: 10.1128/mBio.02103-16.


Structure of the Pseudomonas aeruginosa Type IVa Pilus Secretin at 7.4 Å.

Koo J, Lamers RP, Rubinstein JL, Burrows LL, Howell PL.

Structure. 2016 Oct 4;24(10):1778-1787. doi: 10.1016/j.str.2016.08.007.


Type IV Pilus Alignment Subcomplex Proteins PilN and PilO Form Homo- and Heterodimers in Vivo.

Leighton TL, Yong DH, Howell PL, Burrows LL.

J Biol Chem. 2016 Sep 16;291(38):19923-38. doi: 10.1074/jbc.M116.738377. Epub 2016 Jul 29.


Exopolysaccharide biosynthetic glycoside hydrolases can be utilized to disrupt and prevent Pseudomonas aeruginosa biofilms.

Baker P, Hill PJ, Snarr BD, Alnabelseya N, Pestrak MJ, Lee MJ, Jennings LK, Tam J, Melnyk RA, Parsek MR, Sheppard DC, Wozniak DJ, Howell PL.

Sci Adv. 2016 May 20;2(5):e1501632. doi: 10.1126/sciadv.1501632. eCollection 2016 May.


The Conserved Tetratricopeptide Repeat-Containing C-Terminal Domain of Pseudomonas aeruginosa FimV Is Required for Its Cyclic AMP-Dependent and -Independent Functions.

Buensuceso RN, Nguyen Y, Zhang K, Daniel-Ivad M, Sugiman-Marangos SN, Fleetwood AD, Zhulin IB, Junop MS, Howell PL, Burrows LL.

J Bacteriol. 2016 Jul 28;198(16):2263-74. doi: 10.1128/JB.00322-16. Print 2016 Aug 15.


Biofilm Exopolysaccharides of Pathogenic Fungi: Lessons from Bacteria.

Sheppard DC, Howell PL.

J Biol Chem. 2016 Jun 10;291(24):12529-37. doi: 10.1074/jbc.R116.720995. Epub 2016 Apr 21. Review.


Deacetylation of Fungal Exopolysaccharide Mediates Adhesion and Biofilm Formation.

Lee MJ, Geller AM, Bamford NC, Liu H, Gravelat FN, Snarr BD, Le Mauff F, Chabot J, Ralph B, Ostapska H, Lehoux M, Cerone RP, Baptista SD, Vinogradov E, Stajich JE, Filler SG, Howell PL, Sheppard DC.

mBio. 2016 Apr 5;7(2):e00252-16. doi: 10.1128/mBio.00252-16.


PilN Binding Modulates the Structure and Binding Partners of the Pseudomonas aeruginosa Type IVa Pilus Protein PilM.

McCallum M, Tammam S, Little DJ, Robinson H, Koo J, Shah M, Calmettes C, Moraes TF, Burrows LL, Howell PL.

J Biol Chem. 2016 May 20;291(21):11003-15. doi: 10.1074/jbc.M116.718353. Epub 2016 Mar 28.


Precision-engineering the Pseudomonas aeruginosa genome with two-step allelic exchange.

Hmelo LR, Borlee BR, Almblad H, Love ME, Randall TE, Tseng BS, Lin C, Irie Y, Storek KM, Yang JJ, Siehnel RJ, Howell PL, Singh PK, Tolker-Nielsen T, Parsek MR, Schweizer HP, Harrison JJ.

Nat Protoc. 2015 Nov;10(11):1820-41. doi: 10.1038/nprot.2015.115. Epub 2015 Oct 22.


Characterization of the Pseudomonas aeruginosa Glycoside Hydrolase PslG Reveals That Its Levels Are Critical for Psl Polysaccharide Biosynthesis and Biofilm Formation.

Baker P, Whitfield GB, Hill PJ, Little DJ, Pestrak MJ, Robinson H, Wozniak DJ, Howell PL.

J Biol Chem. 2015 Nov 20;290(47):28374-87. doi: 10.1074/jbc.M115.674929. Epub 2015 Sep 30.


Sph3 Is a Glycoside Hydrolase Required for the Biosynthesis of Galactosaminogalactan in Aspergillus fumigatus.

Bamford NC, Snarr BD, Gravelat FN, Little DJ, Lee MJ, Zacharias CA, Chabot JC, Geller AM, Baptista SD, Baker P, Robinson H, Howell PL, Sheppard DC.

J Biol Chem. 2015 Nov 13;290(46):27438-50. doi: 10.1074/jbc.M115.679050. Epub 2015 Sep 4.


Pel is a cationic exopolysaccharide that cross-links extracellular DNA in the Pseudomonas aeruginosa biofilm matrix.

Jennings LK, Storek KM, Ledvina HE, Coulon C, Marmont LS, Sadovskaya I, Secor PR, Tseng BS, Scian M, Filloux A, Wozniak DJ, Howell PL, Parsek MR.

Proc Natl Acad Sci U S A. 2015 Sep 8;112(36):11353-8. doi: 10.1073/pnas.1503058112. Epub 2015 Aug 26.


The protein BpsB is a poly-β-1,6-N-acetyl-D-glucosamine deacetylase required for biofilm formation in Bordetella bronchiseptica.

Little DJ, Milek S, Bamford NC, Ganguly T, DiFrancesco BR, Nitz M, Deora R, Howell PL.

J Biol Chem. 2015 Sep 11;290(37):22827-40. doi: 10.1074/jbc.M115.672469. Epub 2015 Jul 22.


Identification of Poly-N-acetylglucosamine as a Major Polysaccharide Component of the Bacillus subtilis Biofilm Matrix.

Roux D, Cywes-Bentley C, Zhang YF, Pons S, Konkol M, Kearns DB, Little DJ, Howell PL, Skurnik D, Pier GB.

J Biol Chem. 2015 Jul 31;290(31):19261-72. doi: 10.1074/jbc.M115.648709. Epub 2015 Jun 15.


Enzymatic modifications of exopolysaccharides enhance bacterial persistence.

Whitfield GB, Marmont LS, Howell PL.

Front Microbiol. 2015 May 15;6:471. doi: 10.3389/fmicb.2015.00471. eCollection 2015. Review.


Novel Role for PilNO in Type IV Pilus Retraction Revealed by Alignment Subcomplex Mutations.

Leighton TL, Dayalani N, Sampaleanu LM, Howell PL, Burrows LL.

J Bacteriol. 2015 Jul;197(13):2229-2238. doi: 10.1128/JB.00220-15. Epub 2015 Apr 27.


Direct Staudinger-Phosphonite Reaction Provides Methylphosphonamidates as Inhibitors of CE4 De-N-acetylases.

Ariyakumaran R, Pokrovskaya V, Little DJ, Howell PL, Nitz M.

Chembiochem. 2015 Jun 15;16(9):1350-6. doi: 10.1002/cbic.201500091. Epub 2015 May 26.


Dimeric c-di-GMP is required for post-translational regulation of alginate production in Pseudomonas aeruginosa.

Whitney JC, Whitfield GB, Marmont LS, Yip P, Neculai AM, Lobsanov YD, Robinson H, Ohman DE, Howell PL.

J Biol Chem. 2015 May 15;290(20):12451-62. doi: 10.1074/jbc.M115.645051. Epub 2015 Mar 27.


Biogenesis of Pseudomonas aeruginosa type IV pili and regulation of their function.

Leighton TL, Buensuceso RN, Howell PL, Burrows LL.

Environ Microbiol. 2015 Nov;17(11):4148-63. doi: 10.1111/1462-2920.12849. Epub 2015 Jun 25. Review.


Structural basis for the De-N-acetylation of Poly-β-1,6-N-acetyl-D-glucosamine in Gram-positive bacteria.

Little DJ, Bamford NC, Pokrovskaya V, Robinson H, Nitz M, Howell PL.

J Biol Chem. 2014 Dec 26;289(52):35907-17. doi: 10.1074/jbc.M114.611400. Epub 2014 Oct 30.


P. aeruginosa SGNH hydrolase-like proteins AlgJ and AlgX have similar topology but separate and distinct roles in alginate acetylation.

Baker P, Ricer T, Moynihan PJ, Kitova EN, Walvoort MT, Little DJ, Whitney JC, Dawson K, Weadge JT, Robinson H, Ohman DE, Codée JD, Klassen JS, Clarke AJ, Howell PL.

PLoS Pathog. 2014 Aug 28;10(8):e1004334. doi: 10.1371/journal.ppat.1004334. eCollection 2014 Aug.


A conformational landscape for alginate secretion across the outer membrane of Pseudomonas aeruginosa.

Tan J, Rouse SL, Li D, Pye VE, Vogeley L, Brinth AR, El Arnaout T, Whitney JC, Howell PL, Sansom MS, Caffrey M.

Acta Crystallogr D Biol Crystallogr. 2014 Aug;70(Pt 8):2054-68. doi: 10.1107/S1399004714001850. Epub 2014 Jul 25.


Modification and periplasmic translocation of the biofilm exopolysaccharide poly-β-1,6-N-acetyl-D-glucosamine.

Little DJ, Li G, Ing C, DiFrancesco BR, Bamford NC, Robinson H, Nitz M, Pomès R, Howell PL.

Proc Natl Acad Sci U S A. 2014 Jul 29;111(30):11013-8. doi: 10.1073/pnas.1406388111. Epub 2014 Jul 3.

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