title: Downregulation of Autolysin-Encoding Genes by Phage-Derived Lytic Proteins Inhibits Biofilm Formation in Staphylococcus aureus.
abstract: Phage-derived lytic proteins are a promising alternative to conventional antimicrobials. One of their most interesting properties is that they do not readily select for resistant strains, which is likely due to the fact that their targets are essential for the viability of the bacterial cell. Moreover, genetic engineering allows the design of new "tailor-made" proteins that may exhibit improved antibacterial properties. One example of this is the chimeric protein CHAPSH3b, which consists of a catalytic domain from the virion-associated peptidoglycan hydrolase of phage vB_SauS-phiIPLA88 (HydH5) and the cell wall binding domain of lysostaphin. CHAPSH3b had previously shown the ability to killStaphylococcus aureuscells. Here, we demonstrate that this lytic protein also has potential for the control of biofilm-embeddedS. aureuscells. Additionally, subinhibitory doses of CHAPSH3b can decrease biofilm formation by someS. aureusstrains. Transcriptional analysis revealed that exposure ofS. aureuscells to this enzyme leads to the downregulation of several genes coding for bacterial autolysins. One of these proteins, namely, the major autolysin AtlA, is known to participate in staphylococcal biofilm development. Interestingly, anatlmutant strain did not display inhibition of biofilm development when grown at subinhibitory concentrations of CHAPSH3b, contrary to the observations made for the parental and complemented strains. Also, deletion ofatlled to low-level resistance to CHAPSH3b and the endolysin LysH5. Overall, our results reveal new aspects that should be considered when designing new phage-derived lytic proteins aimed for antimicrobial applications.
authors.affiliation: Instituto de Productos Lácteos de Asturias (IPLA-CSIC), Asturias, Spain lucia.fernandez@ipla.csic.es.
authors.forename: Lucía
authors.initials: L
authors.lastname: Fernández
authors.affiliation: Instituto de Productos Lácteos de Asturias (IPLA-CSIC), Asturias, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: González
authors.affiliation: Instituto de Productos Lácteos de Asturias (IPLA-CSIC), Asturias, Spain.
authors.forename: Ana Belén
authors.initials: AB
authors.lastname: Campelo
authors.affiliation: Instituto de Productos Lácteos de Asturias (IPLA-CSIC), Asturias, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Martínez
authors.affiliation: Instituto de Productos Lácteos de Asturias (IPLA-CSIC), Asturias, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Rodríguez
authors.affiliation: Instituto de Productos Lácteos de Asturias (IPLA-CSIC), Asturias, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: García
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development; D002473:Cell Wall / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D008248:Lysostaphin / Q000378:metabolism; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000235:genetics*; D013204:Staphylococcus Phages / Q000235:genetics*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D014760:Viral Fusion Proteins / Q000235:genetics / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D014760:Viral Fusion Proteins; D010450:Endopeptidases; D008248:Lysostaphin; C001143:endolysin; D009238:N-Acetylmuramoyl-L-alanine Amidase
keywords: biofilms; novel antimicrobials; phage lytic proteins; transcriptional responses to antimicrobials