American Journal of Infectious Diseases 8 (1): 5-12, 2012
ISSN 1553-6203
© 2012 Science Publications
Corresponding Author: Apurb Rashmi Bhengraj, MIcrobiology and Tissue Culture Division, National Institute of Pathology,
Indian Council of Medical Research (ICMR), New Delhi, India
5
Study on Survival of Chlamydia trachomatis
in the Presence of Antichlamydial Drugs
Apurb Rashmi Bhengraj, Pragya Srivastava, Harsh Vardhan,
Suraj Singh Yadav, Laishram Chandreshwor Singh and Aruna Mittal
MIcrobiology and Tissue Culture Division,
National Institute of Pathology,
Indian Council of Medical Research (ICMR), New Delhi, India
Abstract: Problem statement: Recurrent genital Chlamydia trachomatis infections due to treatment
failures may results in complex sequelae leading to reproductive complexity and morbidity. It can be
resulted by the heterotypic resistance with decreased drug susceptibility characteristic of the isolate.
Studies are needed to understand the treatment failures and resistance characteristic of C. trachomatis.
Hence, in vitro study was conducted on C. trachomatis isolate in the presence of antichlamydial drugs.
Approach: Our aim was to study ygeD gene in C. trachomatis clinical isolate having decreased drug
susceptibility profile and to analyze HeLa cells phenotypically upon infection in presence of
antichlamydial drugs. Sequencing was done to check any mutational change (s) in ygeD gene of C.
trachomatis isolate (CT-244), mRNA expression was analyzed in presence of antichlamydial drugs by
Real Time RT-PCR. Transduction study was carried out in infected HeLa cells to detect changes at
cellular level in presence of antichlamydial drugs by transducing with GFP/RFP-tagged proteins and
analyzed by FACS. Results: A point mutation was detected in ygeD gene of C. trachomatis isolate.
Further, mRNA expression level of ygeD gene was observed to be increased at 8 hpi in presence of
doxycycline while in presence of azithromycin it was increased at 24 hpi. GFP-tagged plasma
membrane protein expression in infected HeLa cells found to be reduced as compare to the uninfected
cells. Upon infection, the RFP-tagged actin protein expression was up-regulated in comparison to the
uninfected HeLa cells. No difference in expression of plasma membrane and actin protein was
observed in susceptible serovar D and CT-244 isolate. Conclusion: The present study suggest that C.
trachomatis isolate with decreased drug susceptibility profile may have an active efflux strategy for its
survival in the presence of antichlamydial drugs and it may not affect its host cell plasma membrane or
actin organization for its survival in order to resist the antichlamydial drugs.
Key words: Chlamydia trachomatis, recurrent infection, antimicrobial susceptibility, antichlamydial
drugs, pelvic inflammatory, chlamydial infections, decreased susceptibility, protein
expression
INTRODUCTION
Chlamydia trachomatis an obligatory intracellular
pathogen causes a spectrum of clinically important
chronic inflammatory diseases of human. C.
trachomatis infection is one of the most prevalent
sexually transmitted diseases in the world (Gerbase et
al., 1998; Beagley and Timms, 2000). In females, C.
trachomatis causes cervicitis, urethritis, ectopic
pregnancy, pelvic inflammatory disease, tubal factor
infertility and chronic pelvic pain (Morre et al., 2000).
Studies have also implicated association of C.
trachomatis infection with cervical and ovarian cancer
and increase in HIV infectivity (Luostarinen et al.,
2004). Antibiotics have the major role in treating
chlamydial infections; azithromycin and doxycycline
are considered as first line drugs by the Centers for
Disease control and prevention (CDC) (Workowski and
Berman, 2010). Efficacy of these drugs for treatment of
chlamydial infections are high, however many
researchers report the problem of recurrent infections
and treatment failures Wang et al. (2005). It has also
been reported that in women with persistent or recurrent
infections, the infection can spread upwards from the
endocervix to the fallopian tubes and may result in
infertility or ectopic pregnancy (Hillis et al., 1997).
Recurrent C. trachomatis infections often results from
failure of antibiotic therapy or from reinfection due to