The host factors and their regulatory mechanisms involved in host immune defense against Mycobacterium tuberculosis (Mtb) are largely unexplored, which impedes host-directed therapy (HDT) development in tuberculosis. Prof. WANG Jing and Prof. LIU Cui Hua’s lab at Institute of Microbiology of Chinese Academy of Sciences identify that TRIM27 is the critical host protective factor against Mtb through functioning as a transcription activator of transcription factor EB (TFEB) to enhance autophagy flux, thus providing a potential HDT strategy for tuberculosis treatment.

Microbicide persistence prolongs antimicrobial therapy, leading to relapse after cessation of therapy. By developing single-cell tracking strategies, IMCAS scientists demonstrate that Cryptococcus neoformans can form fungicide-tolerant persisters during lung infection, uncover mechanisms involved, and identify indicator molecules whose abundance in the cryptococcal cell is predictive of fungicidal efficacy. These findings provide evidence for and the determinant of AmB-tolerant persister formation in pulmonary cryptococcosis, which has potential clinical significance.

The gut commensal microbes, represented by Christensenella minuta, alleviated features of metabolic disease in model mice by generating a new class of secondary bile acids with 3-O-acylation substitution that inhibit the intestinal farnesoid X receptor. Our findings underscore the potential of Christensenella minuta and 3-O-acylated bile acids in the treatment and prevention of metabolic diseases, including Type 2 diabetes.

Fungicide tolerance allows fungi to survive fungicide killing, but whether it can be induced by host-derived factors during fungal disease remains unknown. In the leading cause of fungal meningitis, Cryptococcus neoformans, IMCAS scientists found that brain glucose strongly induces fungicide tolerance, limiting the effectiveness of treatment for cryptococcal meningitis. These findings enabled the identification of a drug combination that was more effective against cryptococcal meningitis in mice than clinically recommended therapies.

Ebola virus (EBOV) L polymerase performs de novo replication which is controlled by the specific 3’ leader sequence of EBOV genome. Structural analysis revealed that the 3’ leader RNA binds in the template entry channel with a distinctive stable bend conformation, which is required for the de novo replication activity. These findings have provided a new mechanistic understanding of RNA synthesis for the non-segmented negative-strand RNA virus (nsNSV) including EBOV and revealed important targets for the development of antiviral drugs.