The innate immune protein calprotectin promotes Pseudomonas aeruginosa and Staphylococcus aureus interaction.
Microorganisms form biofilms containing differentiated cell populations. To determine factors driving differentiation, we herein visualize protein and metal distributions within Pseudomonas aeruginosa biofilms using imaging mass spectrometry. These in vitro experiments reveal correlations between differential protein distribution and metal abundance. Notably, zinc- and manganese-depleted portions of the biofilm repress the production of anti-staphylococcal molecules. Exposure to calprotectin (a host protein known to sequester metal ions at infectious foci) recapitulates responses occurring within metal-deplete portions of the biofilm and promotes interaction between P. aeruginosa and Staphylococcus aureus. Consistent with these results, the presence of calprotectin promotes co-colonization of the murine lung, and polymicrobial communities are found to co-exist in calprotectin-enriched airspaces of a cystic fibrosis lung explant. These findings, which demonstrate that metal fluctuations are a driving force of microbial community structure, have clinical implications because of the frequent occurrence of P. aeruginosa and S. aureus co-infections.
Tennessee Valley Healthcare Systems, US Department of Veterans Affairs, Nashville, Tennessee 37212, USA.|Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Catherine A
CA
Wakeman
Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37232, USA.
Jessica L
JL
Moore
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Michael J
MJ
Noto
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Yaofang
Y
Zhang
Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37232, USA.
Marc D
MD
Singleton
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Boone M
BM
Prentice
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Benjamin A
BA
Gilston
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Ryan S
RS
Doster
Tennessee Valley Healthcare Systems, US Department of Veterans Affairs, Nashville, Tennessee 37212, USA.|Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Jennifer A
JA
Gaddy
Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37232, USA.|Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Walter J
WJ
Chazin
Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37232, USA.|Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Richard M
RM
Caprioli
Tennessee Valley Healthcare Systems, US Department of Veterans Affairs, Nashville, Tennessee 37212, USA.|Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Eric P
EP
Skaar
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development; D053898:Biosynthetic Pathways / Q000187:drug effects / Q000235:genetics; D060085:Coinfection / Q000382:microbiology / Q000473:pathology; D003550:Cystic Fibrosis / Q000382:microbiology / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D039841:Leukocyte L1 Antigen Complex / Q000494:pharmacology*; D008345:Manganese / Q000378:metabolism; D051379:Mice; D056265:Microbial Interactions / Q000187:drug effects; D040901:Proteomics; D011552:Pseudomonas Infections / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013203:Staphylococcal Infections / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism
D001426:Bacterial Proteins; D039841:Leukocyte L1 Antigen Complex; D008345:Manganese; D015032:Zinc