PMID- 28973037
OWN - NLM
STAT- MEDLINE
DCOM- 20171019
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 10
DP  - 2017
TI  - Identification of a strong and specific antichlamydial N-acylhydrazone.
PG  - e0185783
LID - 10.1371/journal.pone.0185783 [doi]
AB  - Sexually transmitted Chlamydia trachomatis is an extremely common infection and
      often leads to serious complications including infertility and pelvic
      inflammatory syndrome. Several broad-spectrum antibiotics are currently used to
      treat C. trachomatis. Although effective, they also kill beneficial vaginal
      lactobacilli. Two N-acylhydrazones, CF0001 and CF0002, have been shown previously
      to inhibit chlamydial growth without toxicity to human cells and Lactobacillus
      spp. Of particular significance, the rate of random mutation leading to
      resistance of these inhibitors appears to be extremely low. Here, we report three
      analogs of CF0001 and CF0002 with significantly stronger inhibitory effects on
      chlamydiae. Even though the new compounds (termed SF1, SF2 and SF3) displayed
      slightly decreased inhibition efficiencies for a rare Chlamydia variant selected 
      for CF0001 resistance (Chlamydia muridarum MCR), they completely overcame the
      resistance when used at concentrations of 75-100 muM. Importantly, SF1, SF2 and
      SF3 did not shown any toxic effect on lactobacilli, whereas SF3 was also well
      tolerated by human host cells. An effort to isolate SF3-resistant variants was
      unsuccessful. By comparison, variants resistant to rifampin or spectinomycin were
      obtained from smaller numbers of chlamydiae. Our findings suggest that SF3
      utilizes an antichlamydial mechanism similar to that of CF0001 and CF0002, and
      will be more difficult for chlamydiae to develop resistance to, potentially
      making it a more effective antichlamydial agent.
FAU - Zhang, Huirong
AU  - Zhang H
AD  - Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers, The
      State University of New Jersey, Piscataway, New Jersey, United States of America.
FAU - Kunadia, Anuj
AU  - Kunadia A
AD  - Department of Chemistry and Chemical Biology, School of Arts and Sciences,
      Rutgers, The State University of New Jersey, Piscataway, New Jersey, United
      States of America.
FAU - Lin, Yingfu
AU  - Lin Y
AD  - Department of Chemistry and Chemical Biology, School of Arts and Sciences,
      Rutgers, The State University of New Jersey, Piscataway, New Jersey, United
      States of America.
FAU - Fondell, Joseph D
AU  - Fondell JD
AD  - Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers, The
      State University of New Jersey, Piscataway, New Jersey, United States of America.
FAU - Seidel, Daniel
AU  - Seidel D
AD  - Department of Chemistry and Chemical Biology, School of Arts and Sciences,
      Rutgers, The State University of New Jersey, Piscataway, New Jersey, United
      States of America.
FAU - Fan, Huizhou
AU  - Fan H
AUID- ORCID: http://orcid.org/0000-0002-4903-926X
AD  - Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers, The
      State University of New Jersey, Piscataway, New Jersey, United States of America.
LA  - eng
GR  - R21 AI122034/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20171003
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Anti-Bacterial Agents)
SB  - IM
MH  - Anti-Bacterial Agents/*pharmacology/therapeutic use
MH  - Chlamydia Infections/*drug therapy/microbiology
MH  - Chlamydia muridarum/*drug effects
MH  - Chlamydia trachomatis/*drug effects
MH  - Female
MH  - Humans
MH  - Lactobacillus/*drug effects
MH  - Vagina/drug effects
PMC - PMC5626472
EDAT- 2017/10/04 06:00
MHDA- 2017/10/20 06:00
CRDT- 2017/10/04 06:00
PHST- 2017/05/29 00:00 [received]
PHST- 2017/09/19 00:00 [accepted]
PHST- 2017/10/04 06:00 [entrez]
PHST- 2017/10/04 06:00 [pubmed]
PHST- 2017/10/20 06:00 [medline]
AID - 10.1371/journal.pone.0185783 [doi]
AID - PONE-D-17-20585 [pii]
PST - epublish
SO  - PLoS One. 2017 Oct 3;12(10):e0185783. doi: 10.1371/journal.pone.0185783.
      eCollection 2017.