Enteric bacteria (including some pathogens) have to effectively resist the extremely acidic environment of gastric juice (pH 1-3) for survival and the anti-acid chaperone HdeA plays an important role in this process. CHANG’s group previously reported that the HdeA protein functions via a unique manner of “loss of functions with ordered structure but exhibition of functions with disordered structures” (Hong, 2005, J Biol Chem, 280: 27029; Wu, 2008, Biochem J, 412: 389). Recently, his group applied the unnatural amino acid-mediated in vivo photo-crosslinking method to covalently capture and then identify the client proteins of HdeA in living cells under extreme acidic conditions, uncovering a unique chaperone-protecting-chaperone mechanism for the bacterial acid resistance (as schematically illustrated below). This work is of importance for understanding the pathogenic mechanism of a variety of enteric pathogens including E. coli and was published as a cover article on Nature Chemical Biology (Zhang, 2011, 7: 671).Later, Professor CHANG was invited by the prestigious journal 《Trends in Microbiology》 to write a review article on the mechanism of bacterial acid resistance (Hong etal., Trends Microbiol, 2012). In addition, CHNAG’s group unraveled the mechanism of small heat shock protein in interacting with natural substrates proteins in living cells (Fu et al., J Biol Chem, 2013a, 2013b) and the action mechanism of protein quality control factors DegP and FkpA in the biogenesis of outer membrane proteins (Ge et al, FEBS J, 2014; J Bacteriol, 2014.). They found that nematode small heat shock protein Hsp17 enabled E. coli to grow at 50°C (Ezemaduka et al,. J Bacteriol., 2014), which is the highest growth temperature of E. coli ever reported. Lastly, they observed that Hsp17 exhibited the chaperone activity by forming a super-complex (Zhang et al., Sci Rep, 2015) and discovered that hypoionic shock treatment enabled aminoglycosides to eradicate antibiotic-tolerant bacteria (Liu et al., Sci Rep, 2015).

This lab also revealed that a supercomplex spanning the inner and outer membranes mediates the biogenesis of β-barrel outer membrane proteins in bacteria based on studies mainly performed with unnatural amino acid-mediated in vivo protein photocrosslinking analysis (Wang et al. JBC, 2016). With this approach, they also unveiled a shortened version of the SecA protein, termed SecAN, function as the protein-conducting channel for nascent β-barrel outer membrane proteins. Additionally, they accidentally discovered a reversible protein sequestering subcellular structure, termed, quiescent body, that are formed only in the non-growing non-piding bacterial cells.

Yang Liu, Chunyan Yu, Huijia Yin, Qingfang Zeng, Mengyuan Wang, Hongfei Li，Ying Zhao, Peining Chen, Zhiyi Zhao