David Evans, BSC, PhD

Areas of Expertise

Biological & Pharmaceutical Sciences

Biography

I have always been interested in the pathogenesis of infections from microbial toxins to virulence strategies that microbes use when encountering the host. Along with those interests came an understanding and appreciation for host immunity ranging from constitutive defenses to adaptive responses. My research involvement in studying the pathogenesis of Pseudomonas aeruginosa corneal infections is well aligned with those interests and studying specifics of contact lens-related corneal infection by P. aeruginosa has helped shed light on broader aspects of bacterial virulence and host immunity. The cornea is an ideal model for investigating bacterial-host interactions. My research in collaboration with Dr. Suzanne Fleiszig at the School of Optometry, University of California Berkeley, has focused on both sides of those interactions; 1) the role of bacterial virulence mechanisms in finding a way for bacteria to survive/adapt, colonize the corneal epithelium, invade and traverse epithelial barriers, and avoid phagocytosis by immune cells, and 2) the nature of corneal defenses that make it an inhospitable mucosal surface for microbial survival, colonization and virulence. The latter includes numerous studies of role of tear fluid in protecting the ocular surface, the role of epithelial barrier integrity and epithelial-derived antimicrobials in defending the cornea, and the role of resident and infiltrating immune cells in maintaining corneal barrier function.

Education

• BSc [Pharmacy] and PhD. University of Manchester, United Kingdom

Recent Publications

1.     Gilbert P, Allison DG, Evans DJ, Handley PS, Brown MRW. Growth rate control of adherent bacterial populations. Applied and Environmental Microbiology, 1989: 55; 1308-11

2.     Allison DG, Evans DJ, Brown MRW, Gilbert P. Possible involvement of the division cycle in dispersal of Escherichia coli from biofilms. Journal of Bacteriology, 1990: 172; 1667-9

3.     Evans DJ, Brown MRW, Allison DG, Gilbert P. Susceptibility of bacterial biofilms to tobramycin: role of specific growth rate and phase in the division cycle. Journal of Antimicrobial Chemotherapy, 1990: 25; 585-91

4.     Evans DJ, Allison DG, Brown MRW, Gilbert P. Effect of growth rate on resistance of Gram-negative biofilms to cetrimide. Journal of Antimicrobial Chemotherapy, 1990: 26; 473-8

5.     Allison DG, Brown MRW, Evans DJ, Gilbert P. Surface hydrophobicity and dispersal of Pseudomonas aeruginosa from biofilms. FEMS Microbiology Letters, 1990: 71; 101-4

6.     Evans DJ, Allison DG, Brown MRW, Gilbert P. Susceptibility of Pseudomonas aeruginosa  and Escherichia coli biofilms towards ciprofloxacin: effect of specific growth rate. Journal of Antimicrobial Chemotherapy, 1991: 27; 177-84

7.     Gilbert P, Evans DJ, Evans E, Duguid IG, Brown MRW. Surface characteristics and adhesion of Escherichia coli and Staphylococcus epidermidis. Journal of Applied Bacteriology, 1991: 71; 72-7

8.     Hodgson A, Evans DJ, Brown MRW, Gilbert P. Involvement of cellular division cycle in the susceptibility of Escherichia coli to cold- and osmotic shock. Microbios, 1992: 72; 175-82

9.     Gilbert P, Evans DJ, Brown MRW. Formation and dispersal of bacterial biofilms in-vivo and in-situ. Journal of Applied Bacteriology, 1993. 74: 67-78S

10.     Evans DJ, Pier GB, Coyne MJ Jr, Goldberg JB. The rfb locus from Pseudomonas aeruginosa strain PA103 promotes the expression of O antigen by both LPS-rough and LPS-smooth isolates from cystic fibrosis patients. Molecular Microbiology, 1994: 13; 427-34

11.     Meluleni GJ, Grout M, Evans DJ, Pier GB. Mucoid Pseudomonas aeruginosa growing in a biofilm in-vitro are killed by opsonic antibodies to the mucoid exopolysaccharide capsule but not by antibodies produced during chronic lung infection in cystic fibrosis patients. Journal of Immunology, 1995: 155; 2029-38

12.     Fleiszig SMJ, Zaidi TS, Preston MJ, Grout M, Evans DJ, Pier GB. Cytotoxicity and corneal epithelial cell invasion by isolates of Pseudomonas aeruginosa. Infection and Immunity, 1996: 64; 2288-94

13.     Fleiszig SMJ, Evans DJ, Zaidi TS, Mowrey-McKee MF, Payor RE, Vallas V, Muller E, Pier GB.  Factors affecting Staphylococcus epidermidis adhesion to contact lenses. Optometry and Vision Science, 1996: 73; 590-4

14.     Fleiszig SMJ, Evans DJ, Do N, Vallas V, Shin S, Mostov K. Epithelial cell polarity affects susceptibility to Pseudomonas aeruginosa invasion and cytotoxicity. Infection and Immunity, 1997: 65; 2861-7

15.     Evans DJ, Frank DW, Finck-Barbancon V, Wu C, Fleiszig SMJ. Pseudomonas aeruginosa invasion and cytotoxicity are independent events, both of which involve protein tyrosine kinase activity. Infection and Immunity, 1998: 66; 1453-9

16.     Evans DJ, Matsumoto PS, Widdicombe JH, Li-Yun C, Maminishkis AA, Miller SS. Pseudomonas aeruginosa induces changes in fluid transport across airway surface epithelia. American Journal of Physiology [Cell Physiology], 1998: 275; C1284-90

17.     Lee A, Chow D, Haus B, Tseng W, Evans DJ, Fleiszig S, Chandy G, Machen T. Airway epithelial tight junctions and binding and cytotoxicity of Pseudomonas aeruginosa. American Journal of Physiology [Lung Cellular and Molecular Physiology], 1999: 277; L204-17

18.      Dean CR, Franklund CV, Retief JD, Coyne MJ Jr, Hatano K, Evans DJ, Pier GB, Goldberg JB.  Characterization of the serogroup O11 O-antigen locus of Pseudomonas aeruginosa PA103. Journal of Bacteriology, 1999: 181; 4275-84

19.     Fleiszig SMJ, Evans DJ. The pathogenesis of bacterial keratitis: studies with Pseudomonas aeruginosa. Clinical and Experimental Optometry, 2002: 85; 271-78

20.     Evans DJ, Maltseva IA, Wu J, Fleiszig SMJ. Pseudomonas aeruginosa internalization by corneal epithelial cells involves MEK and ERK signal transduction proteins. FEMS Microbiology Letters, 2002: 213; 73-9

21.     Evans DJ, Kuo TC, Kwong M, Van R, Fleiszig, SMJ. Mutation of csk, encoding the C-terminal Src kinase, reduces Pseudomonas aeruginosa internalization by mammalian cells and enhances bacterial cytotoxicity. Microbial Pathogenesis, 2002: 33; 135-43

22.     Evans DJ, Kuo T, Kwong M, Van R, Fleiszig SMJ. Pseudomonas aeruginosa strains with lipopolysaccharide defects exhibit reduced intracellular viability after invasion of corneal epithelial cells. Experimental Eye Research, 2002: 75; 635-43

23.         Fleiszig SMJ, McNamara NA, Evans DJ. The tear film and defense against infection. Advances in Experimental Medicine and Biology, 2002: 506; 523-30

24.     Fleiszig SMJ, Kwong M, Evans DJ. Modification of Pseudomonas aeruginosa interactions with corneal epithelial cells by human tear fluid. Infection and Immunity, 2003: 71; 3866-74 

25.     Fleiszig SMJ, Evans DJ. Contact Lens Infections: Can they ever be eradicated? Eye and Contact Lens, 2003: 29; S67-71

26.     Lee EJ, Cowell BA, Evans DJ, Fleiszig SMJ. Contribution of ExsA-regulated factors towards corneal infection by cytotoxic and invasive Pseudomonas aeruginosa in a murine scarification model. Investigative Ophthalmology and Visual Science, 2003: 44; 3892-98 

27.    Zolfaghar I, Evans DJ, Fleiszig SMJ. Twitching motility contributes to the role of pili in corneal infection caused by Pseudomonas aeruginosa. Infection and Immunity, 2003: 71; 5389-93

28.     Lee EJ, Evans DJ, Fleiszig SMJ. Role of Pseudomonas aeruginosa ExsA in penetration through corneal epithelium in a novel in vivo model. Investigative Ophthalmology and Visual Science, 2003: 44; 5220-27

29.     Ni M, Evans DJ, Hawgood S, Anders EM, Sack RA, Fleiszig SMJ. Surfactant protein D is present in human tear fluid and the cornea and inhibits epithelial cell invasion by Pseudomonas aeruginosa. Infection and Immunity, 2005: 73; 2147-56

30.         Cowell BA, Evans DJ, Fleiszig SMJ. Actin cytoskeleton disruption by ExoY and its effects on Pseudomonas aeruginosa invasion. FEMS Microbiology Letters. 2005: 250; 71-6

31.     Zolfaghar I, Angus AA, Kang PJ, To A, Evans DJ, Fleiszig SMJ. Mutation of retS, encoding a putative hybrid two-component regulatory protein in Pseudomonas aeruginosa, attenuates multiple virulence mechanisms. Microbes and Infection, 2005: 7; 1305-16

32.     Zolfaghar I, Evans DJ, Ronaghi R, Fleiszig SMJ. Type III-secretion-dependent modulation of innate immunity as one of multiple factors regulated by Pseudomonas aeruginosa RetS. Infection and Immunity, 2006: 74; 3880-9

33.     Kwong MSF, Evans DJ, Ni M, Cowell BA, Fleiszig SMJ. Human tear fluid protects against Pseudomonas aeruginosa keratitis in a murine experimental model. Infection and Immunity, 2007: 75; 2325-32 

34.     Maltseva I, Fleiszig SMJ, Evans DJ, Kerr, S, Sidhu S, McNamara NA, Basbaum C. Exposure of human corneal epithelial cells to contact lenses in vitro suppresses the upregulation of human beta-defensin-2 in response to antigens of Pseudomonas aeruginosa. Experimental Eye Research, 2007: 85; 142-53

35.     Evans DJ, McNamara NA, Fleiszig SMJ. Bacterial keratitis: Dissecting host-pathogen interactions at the ocular surface. Ocular Surface Journal, 2007: 5; 213-27

36.     Tam C, Lewis S, Li W, Lee E, Evans DJ, Fleiszig SMJ. Mutation of the phospholipase catalytic domain of the Pseudomonas aeruginosa cytotoxin ExoU abolishes colonization promoting activity and reduces corneal disease severity. Experimental Eye Research, 2007: 85; 799-805

37.     Angus AA, Ackerman-Lee A, Augustin DK, Lee EJ, Evans DJ, Fleiszig SMJ. Pseudomonas aeruginosa induces membrane blebs in epithelial cells which are utilized as a niche for intracellular replication and motility. Infection and Immunity, 2008: 76; 1992-2001

38.     Ni M, Tam C, Verma A, Ramphal R, Hawgood S, Evans DJ, Fleiszig SMJ. Expression of surfactant protein D in human corneal epithelial Cells is upregulated by Pseudomonas aeruginosa. FEMS Immunology and Medical Microbiology, 2008: 54; 177-84

39.     Thompson DF, Farmer KC, Beall DG, Evans DJ, Melchert RB, Ross LA, Schmoll BJ. Identifying perceptions of professionalism in pharmacy using a four-frame leadership model. American Journal of Pharmaceutical Education, 2008: 72; Article 90 

40.    Alarcon I, Evans DJ, Fleiszig SMJ. The Role of twitching motility in Pseudomonas aeruginosa exit from and translocation of corneal epithelial cells. Investigative Ophthalmology and Visual Science, 2009: 50; 2237-44

41.    Mun JJ, Tam C, Kowbel D, Hawgood S, Barnett MJ, Evans DJ, Fleiszig SMJ. Clearance of Pseudomonas aeruginosa from a healthy ocular surface involves surfactant protein-D and is compromised by bacterial elastase in a murine “null-infection” model. Infection and Immunity, 2009: 77; 2392-8

42.    Alarcon I, Kwan L, Yu C, Evans DJ, Fleiszig SMJ. The role of corneal epithelial basement membrane in ocular defense against Pseudomonas aeruginosa. Infection and Immunity, 2009: 77; 3264-71

43.    Mészáros K, Barnett MJ, McDonald K, Wehring H, Evans DJ, Sasaki-Hill D, Goldsmith PC, Knapp KK. Progress Examination for assessing students’ readiness for Advanced Pharmacy Practice Experiences. American Journal of Pharmaceutical Education, 2009: 73; Article 109

44.     Tam C, Mun JJ, Evans DJ, Fleiszig SMJ. The impact of inoculation parameters on the pathogenesis of contact lens-related infectious keratitis. Investigative Ophthalmology and Visual Science, 2010: 51; 3100-6

45.     Fleiszig SMJ, Evans DJ. Pathogenesis of contact lens-associated microbial keratitis. Optometry and Vision Science, 2010: 87; 225-32. Letter to Editor, Fleiszig SMJ, Evans, DJ. Optometry & Vision Science, 2010: 87; 613-14

46.     Angus AA, Evans DJ, Barbieri JT, Fleiszig SMJ. The ADP-Ribosylation Domain of Pseudomonas aeruginosa ExoS is required for membrane bleb-niche formation and bacterial survival within epithelial cells. Infection and Immunity, 2010: 78; 5400-10

47.     Augustin DK, Heimer SR, Tam C, Li W, LeDue J, Evans DJ, Fleiszig SMJ. Role of defensins in corneal epithelial barrier function against P. aeruginosa traversal. Infection and Immunity, 2011: 79; 595-605

48.     Alarcon I, Tam C, Mun J, LeDue J, Evans DJ, Fleiszig SMJ. Factors impacting corneal epithelial barrier function against Pseudomonas aeruginosa traversal. Investigative Ophthalmology and Visual Science, 2011: 52; 1368-77

49.     Tran VB, Fleiszig SMJ, Evans DJ, Radke CJ. Dynamics of flagellar and pilus-mediated Pseudomonas aeruginosa surface association with contact lenses. Applied and Environmental Microbiology, 2011: 77; 3644-52

50.     Tran VB, Sung YS, Fleiszig SMJ, Evans DJ, Radke CJ. Dynamics of Pseudomonas aeruginosa association with anionic hydrogel surfaces in the presence of aqueous divalent-cation salts. Journal of Colloid and Interface Science, 2011: 362; 58-66

51.      Mun JJ, Tam C, Evans DJ, Fleiszig SMJ. Modulation of epithelial immunity by mucosal fluid. Nature Scientific Reports, 2011: 1; Article 8

52.     Hritonenko V, Mun J, Tam C, Simon NC, Barbieri JT, Evans DJ, Fleiszig SMJ. Adenylate cyclase activity of Pseudomonas aeruginosa ExoY can mediate bleb-niche formation in epithelial cells and contributes to virulence. Microbial Pathogenesis. 2011: 51; 305-12

53.     Tam C, LeDue J, Mun JJ, Herzmark P, Robey EA, Evans DJ, Fleiszig SMJ. 3D quantitative imaging of unprocessed live tissue reveals epithelial defense against bacterial adhesion and subsequent traversal requires MyD88. PLoS ONE. 2011: 6; e24008

54.     Ramirez J, Fleiszig SMJ, Sullivan AB, Tam C, Borazjani R, Evans DJ. Traversal of multilayered corneal epithelia by cytotoxic Pseudomonas aeruginosa requires the phospholipase domain of ExoU. Investigative Ophthalmology and Visual Science. 2012: 53; 448-53

55.     Hritonenko V, Evans DJ, Fleiszig SMJ. Translocon-independent intracellular replication by Pseudomonas aeruginosa requires the ADP-ribosylation domain of ExoS. Microbes and Infection. 2012: 14; 1366-73

56.     Tam C, Mun JJ, Evans DJ, Fleiszig SMJ. Cytokeratins mediate epithelial innate defense through their antimicrobial properties. Journal of Clinical Investigation. 2012: 122; 3665-77

57.     Evans DJ and Fleiszig SMJ. Microbial keratitis: could contact lens material affect disease pathogenesis? Eye and Contact Lens. 2013: 39; 72-7

58.     Mun JJ, Tam C, Chan G, Kim, JH, Evans DJ, Fleiszig SMJ. MicroRNA-762 is upregulated in human corneal epithelial cells in response to tear Fluid and Pseudomonas aeruginosa antigens and negatively regulates the expression of host defense genes encoding RNase7 and ST2. PLoS ONE. 2013: 8; e57850

59.     Evans DJ and Fleiszig SMJ. Perspective. Why does the healthy cornea resist Pseudomonas aeruginosa infection? American Journal of Ophthalmology. 2013: 155; 961-70

60.     Heimer SR, Evans DJ, Mun JJ, Stern ME, Fleiszig SMJ. Surfactant protein D contributes to ocular defense against Pseudomonas aeruginosa colonization in a murine model of dry eye disease. PLoS ONE. 2013: 8; e65797

61.     Heimer SR, Evans DJ, Stern ME, Barbieri JT, Yahr T, Fleiszig SMJ. Pseudomonas aeruginosa utilizes the type III secreted toxin ExoS to avoid acidified compartments within epithelial cells. PLoS ONE. 2013: 8; e73111

62.     Borkar DS, Acharya NR, Leong  C, Lalitha  P, Srinivasan  M, Oldenburg CE, Cevallos  V, Lietman TM, Evans DJ, Fleiszig SMJ. Cytotoxic clinical isolates of Pseudomonas aeruginosa identified during the Steroids for Corneal Ulcers Trial show elevated resistance to fluoroquinolones. BMC Ophthalmology. 2014:14; 54

63.      Jolly AL, Takawira D, Oke O, Whiteside SA, Chang SW, Wen ER, Quach K, Evans DJ, Fleiszig SMJ. Pseudomonas aeruginosa-induced bleb-niche formation in epithelial cells is independent of actinomyosin contraction and enhanced by loss of CFTR osmoregulatory function. mBio. 2015: 6; e02533-14

64.     Sullivan AB, Tam C, Metruccio MME, Evans DJ, Fleiszig SMJ. The Importance of the Pseudomonas aeruginosa type three secretion system in epithelium traversal depends upon conditions of host susceptibility. Infection and Immunity. 2015: 83; 1629-40  

65.     Wu YT, Zhu LS, Tam C, Evans DJ, Fleiszig SMJ. P. aeruginosa survival at posterior contact lens surfaces after daily wear. Optometry and Vision Science. 2015: 92; 659-64  

66.     Metruccio MME, Evans DJ, Gabriel MM, Kadurugamuwa JL, Fleiszig SMJ. Pseudomonas aeruginosa outer membrane vesicles triggered by human mucosal fluid and lysozyme can prime host tissue surfaces for bacterial adhesion. Frontiers in Microbiology. 2016: 7; 00871

67.     Sorenson AL, Sorenson RL, Evans DJ. Toxic anterior segment syndrome caused by autoclave reservoir wall biofilms and their residual toxins. Journal of Cataract and Refractive Surgery. 2016: 42;1602-14

68.  Wu YT, Tam C, Zhu LS, Evans DJ, Fleiszig SM. Human tear fluid reduces culturability of contact lens-associated Pseudomonas aeruginosa biofilms but induces expression of the virulence-associated type III secretion system. Ocular Surface Journal. 2017: 15; 88-96

69.     Jolly AL, Agarwal P, Metruccio MME, Spiciarich DR, Evans DJ, Bertozzi CR, Fleiszig SMJ. Corneal surface glycosylation is modulated by IL-1R and Pseudomonas aeruginosa challenge but is insufficient for inhibiting bacterial binding. FASEB J. 2017: 31; 2393-2404.

70.     Li J, Metruccio MME, Smith BE, Evans DJ, Fleiszig SMJ. Mucosal fluid glycoprotein DMBT1 suppresses twitching motility and virulence of the opportunistic pathogen Pseudomonas aeruginosa. PLoS Pathogens. 2017: e1006392

71.     Metruccio MME, Tam C, Evans DJ, Xie A, Stern ME, Fleiszig SMJ. Contributions of MyD88-dependent receptors and CD11c-positive cells to epithelial barrier function against Pseudomonas aeruginosa. Scientific Reports. 2017: 7; 13829

72.     Hritonenko V, Metruccio MME, Evans DJ, Fleiszig SMJ. Epithelial cell lysates ¬¬induce ExoS expression and secretion by Pseudomonas aeruginosa. FEMS Microbiology Letters. 2018: 365; doi: 10.1093/femsle/fny053
 
73.     Smith BE, Li J, Metruccio MME, Wan S, Evans DJ, Fleiszig SMJ. Quantification of bacterial twitching motility in dense colonies using transmitted light microscopy and computational image analysis. Bio-protocol. 2018: 8; e2804

74.     Kroken AR, Chen C, Evans DJ, Yahr TL, Fleiszig SMJ. The impact of ExoS on Pseudomonas aeruginosa internalization by epithelial cells is independent of fleQ and correlates with bistability of type three secretion system gene expression. mBio. 2018: 9; e00668-18

75.     Wan S, Sullivan A, Shieh P, Metruccio MME, Bertozzi C, Evans DJ, Fleiszig SMJ. IL-1R and MyD88 contribute to the absence of a bacterial microbiome on the healthy murine cornea. Frontiers in Microbiology. 2018: 9; 1117

76.     Wu YT, Truong TN, Tam C, Mendoza MN, Zhu LS, Evans DJ, Fleiszig SMJ. Impact of topical corticosteroid pretreatment on susceptibility of the injured murine cornea to Pseudomonas aeruginosa colonization and infection. Experimental Eye Research. 2019: 179; 1-7

77.     Metruccio MME, Wan SJ, Horneman H, Kroken AR, Sullivan AB, Truong TN, Mun JJ, Tam C, Frith R, Welsh L, George MD, Morris CA, Evans DJ, Fleiszig SMJ. A novel murine model for contact lens wear reveals clandestine IL-1R dependent corneal parainflammation and susceptibility to microbial keratitis upon inoculation with Pseudomonas aeruginosa. Ocular Surface Journal. 2019: 17; 119-33

78.     Nieto V, Kroken AR, Grosser MR, Smith BE, Metruccio MME, Hagan PM, Hallsten ME, Evans DJ, Fleiszig SMJ. Type IV pili can mediate bacterial motility within epithelial cells. mBio. 2019: 10; e02880-18

79.     Li J, Wan SJ, Metruccio MME, Ma S, Nazmi K, Bikker FJ, Evans DJ, Fleiszig SMJ. DMBT1 inhibition of Pseudomonas aeruginosa twitching motility involves its N-glycosylation and is independent of the Scavenger Receptor Cysteine-Rich bacteria-binding peptide domain. Scientific Reports. 2019: 9; 13146 

80.     Fleiszig SMJ, Kroken AR, Nieto V, Grosser MR, Wan SJ, Metruccio MME, Evans DJ. Contact lens-related corneal infection: Intrinsic resistance and its compromise. Progress in Retinal and Eye Research. 2020: 76; 100804

81.      Sorenson AL, Holland S, Tran K, Evans DJ, Lin MC, Mamalis N, Chang DF. DLK associated with table-top autoclave biofilms: case series and review. Journal of Cataract and Refractive Surgery. 2020: 46; 340-9

82.    Wan SJ, Ma S, Evans DJ, Fleiszig SMJ. Resistance of the murine cornea to bacterial colonization during experimental dry eye. PLoS ONE. 2020:15; e0234013

83.     Smith B, Datta A, Lee J, Evans DJ, Fleiszig SMJ. Quantification of relative neurite tortuosity using Fourier transforms. Journal of Neuroscience Methods. 2021: 361; 109266.

84.     Tabor LM, Grosser MR, Metruccio MME, Kumar NG, Wu YT, Nieto V, Evans DJ, Fleiszig SMJ. Human tear fluid modulates the Pseudomonas aeruginosa transcriptome to alter antibiotic susceptibility. Ocular Surface Journal. 2021: 22; 94-102. 

85.     Wan SJ, Datta A, Flandrin O, Metruccio MME, Ma S, Nieto N, Kroken AR, Hill RZ, Bautista DM, Evans DJ,  Fleiszig SMJ. Nerve-associated transient receptor potential ion channels can contribute to intrinsic resistance to bacterial adhesion in vivo. FASEB J. 2021: 35; e21899. 

Teaching Responsibilities

Prmc 601, 605, 609, 613