In silico prediction and prioritization of novel selective antimicrobial drug targets in escherichia coli
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In silico prediction and prioritization of novel selective antimicrobial drug targets in escherichia coli. / Svanberg Frisinger, Frida; Jana, Bimal; Donadio, Stefano; Guardabassi, Luca.
In: Antibiotics, Vol. 10, No. 6, 632, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - In silico prediction and prioritization of novel selective antimicrobial drug targets in escherichia coli
AU - Svanberg Frisinger, Frida
AU - Jana, Bimal
AU - Donadio, Stefano
AU - Guardabassi, Luca
N1 - Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021
Y1 - 2021
N2 - Novel antimicrobials interfering with pathogen-specific targets can minimize the risk of perturbations of the gut microbiota (dysbiosis) during therapy. We employed an in silico approach to identify essential proteins in Escherichia coli that are either absent or have low sequence identity in seven beneficial taxa of the gut microbiota: Faecalibacterium, Prevotella, Ruminococcus, Bacteroides, Lactobacillus, Lachnospiraceae and Bifidobacterium. We identified 36 essential proteins that are present in hyper-virulent E. coli ST131 and have low similarity (bitscore < 50 or identity < 30% and alignment length < 25%) to proteins in mammalian hosts and beneficial taxa. Of these, 35 are also present in Klebsiella pneumoniae. None of the proteins are targets of clinically used antibiotics, and 3D structure is available for 23 of them. Four proteins (LptD, LptE, LolB and BamD) are easily accessible as drug targets due to their location in the outer membrane, especially LptD, which contains extracellular domains. Our results indicate that it may be possible to selectively interfere with essential biological processes in Enterobacteriaceae that are absent or mediated by unrelated proteins in beneficial taxa residing in the gut. The identified targets can be used to discover antimicrobial drugs effective against these opportunistic pathogens with a decreased risk of causing dysbiosis.
AB - Novel antimicrobials interfering with pathogen-specific targets can minimize the risk of perturbations of the gut microbiota (dysbiosis) during therapy. We employed an in silico approach to identify essential proteins in Escherichia coli that are either absent or have low sequence identity in seven beneficial taxa of the gut microbiota: Faecalibacterium, Prevotella, Ruminococcus, Bacteroides, Lactobacillus, Lachnospiraceae and Bifidobacterium. We identified 36 essential proteins that are present in hyper-virulent E. coli ST131 and have low similarity (bitscore < 50 or identity < 30% and alignment length < 25%) to proteins in mammalian hosts and beneficial taxa. Of these, 35 are also present in Klebsiella pneumoniae. None of the proteins are targets of clinically used antibiotics, and 3D structure is available for 23 of them. Four proteins (LptD, LptE, LolB and BamD) are easily accessible as drug targets due to their location in the outer membrane, especially LptD, which contains extracellular domains. Our results indicate that it may be possible to selectively interfere with essential biological processes in Enterobacteriaceae that are absent or mediated by unrelated proteins in beneficial taxa residing in the gut. The identified targets can be used to discover antimicrobial drugs effective against these opportunistic pathogens with a decreased risk of causing dysbiosis.
KW - Antimicrobial targets
KW - Escherichia coli
KW - In silico
KW - Microbiota
U2 - 10.3390/antibiotics10060632
DO - 10.3390/antibiotics10060632
M3 - Journal article
C2 - 34070637
AN - SCOPUS:85107646891
VL - 10
JO - Antibiotics
JF - Antibiotics
SN - 2079-6382
IS - 6
M1 - 632
ER -
ID: 273299340