Akt Phosphorylation Influences Persistent Chlamydial Infection and Chlamydia-Induced Golgi Fragmentation Without Involving Rab14.

Xiaobao Huang,Wenjing Li,Mingna Liu,Huiling Zhu,Zhenjian He,Jinfeng Tan,Jiande Han,Chunguang Ma,Xiaohong Chen

doi:10.3389/fcimb.2021.675890

Abstract

Chlamydia trachomatis is an obligate intracellular bacterium that causes multiple diseases involving the eyes, gastrointestinal tract, and genitourinary system. Previous studies have identified that in acute chlamydial infection, C. trachomatis requires Akt pathway phosphorylation and Rab14-positive vesicles to transmit essential lipids from the Golgi apparatus in survival and replication. However, the roles that Akt phosphorylation and Rab14 play in persistent chlamydial infection remain unclear. Here, we discovered that the level of Akt phosphorylation was lower in persistent chlamydial infection, and positively correlated with the effect of activating the development of Chlamydia but did not change the infectivity and 16s rRNA gene expression. Rab14 was found to exert a limited effect on persistent infection. Akt phosphorylation might regulate Chlamydia development and Chlamydia-induced Golgi fragmentation in persistent infection without involving Rab14. Our results provide a new insight regarding the potential of synergistic repressive effects of an Akt inhibitor with antibiotics in the treatment of persistent chlamydial infection induced by penicillin.

Highlights

Chlamydia trachomatis (C. trachomatis) is an obligate intracellular bacterium that can cause several diseases and sequelae in human beings
Extracellular bacteria were removed by aspirating the supernatant followed by the addition of fresh medium supplemented with 10% fetal bovine serum (FBS) and 0.5% glucose, and the cells were maintained under the same conditions until they were harvested at different time points
Our findings revealed that Akt phosphorylation is dynamic during different stages of chlamydial infection, and the level had a robust decrease in persistent infection

Summary

Introduction

Chlamydia trachomatis (C. trachomatis) is an obligate intracellular bacterium that can cause several diseases and sequelae in human beings. When the normal life cycle is disturbed by a variety of stresses, such as amino acid deficiency (Beatty et al, 1994), nutrient depletion (Capmany and Damiani, 2010), antibiotics (Zhu et al, 2014; Xue et al, 2017), immunological factors, and interferon-gamma (IFN-g) (Beatty et al, 1993), the inclusions become smaller and harbor aberrant reticulate bodies (ABs), with slow metabolism and weakened infectivity This results in persistent chlamydial infection, which is thought to be associated with female infertility (Witkin et al, 2017). Due to the difficulty of diagnosis and resistance to antibiotics, persistent infection remains a public health problem (Patton et al, 1994)

Methods

Results

Conclusion