Genomics

Dataset Information

35

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 (PG) hydrolase of phage vB_SauS-phiIPLA88 (HydH5) and the cell wall binding domain of lysostaphin. CHAPSH3b had previously shown the ability to kill S. aureus cells. Here, we demonstrate that this lytic protein also has potential for the control of biofilm-embedded S. aureus cells. Additionally, subinhibitory doses of CHAPSH3b can decrease biofilm formation by some S. aureus strains. Transcriptional analysis revealed that exposure of S. aureus cells 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, an atl mutant 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 of atl led to low-level resistance to CHAPSH3b and endolysin LysH5. Overall, our results reveal new aspects that should be considered when designing new phage-derived lytic proteins aimed for antimicrobial applications. Overall design: 6 samples were analyzed, corresponding to 3 biological replicates of two different conditions (biofilm sample treated with endolysin LysH5 and control biofilm).

INSTRUMENT(S): Illumina HiSeq 2000 (Staphylococcus aureus)

SUBMITTER: Lucia Fernandez  

PROVIDER: GSE94512 | GEO | 2017-03-16

SECONDARY ACCESSION(S): PRJNA370921

REPOSITORIES: GEO

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Publications

Downregulation of Autolysin-Encoding Genes by Phage-Derived Lytic Proteins Inhibits Biofilm Formation in Staphylococcus aureus.

Fernández Lucía L   González Silvia S   Campelo Ana Belén AB   Martínez Beatriz B   Rodríguez Ana A   García Pilar P  

Antimicrobial agents and chemotherapy 20170424 5


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 ca  ...[more]

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