Yarong Wu - Academia.edu (original) (raw)

Papers by Yarong Wu

Zoonoses, Jan 19, 2023

Human plague, caused by Yersinia pestis, a bacterium which first and foremost occurs in wildlife ... more Human plague, caused by Yersinia pestis, a bacterium which first and foremost occurs in wildlife rodent species but occasionally spills over to people: hence the title "Yersinia pestis and Plague". Plague has brought about three pandemics in history, including the first pandemic Justinian plague (from around 541 CE), the second Black Death (from around 1347 CE), and the third modern plague (from around 1880 CE). Since the etiologic agent for plague was identified by Dr. Alexander Yersin during the third pandemic in Hong Kong of China in 1894 [1], more than 120 years have passed, and we have a better understanding of the physiology, pathogenesis, and evolution of Y. pestis. We have developed technologies for plague diagnosis and treatment. Plague is effectively controlled in most endemic regions, except some parts of Africa. The wide distribution of natural plague foci in Asia, Eurasia, Africa, and the Americas, with occasional occurrences in both rodents and humans or following long-distance travel of plague-infected individuals into large cities reminds us of the threat of a plague outbreak. In this review, we will summarize what we know and what we do not know about plague and its causative agent, Y. pestis. The key issues that need to be resolved are also included (Box).

Emerging Microbes & Infections, 2022

Colistin is regarded as a last-resort agent to combat infections caused by multidrug-resistant (M... more Colistin is regarded as a last-resort agent to combat infections caused by multidrug-resistant (MDR) Gram-negative bacteria, especially carbapenem-resistant isolates. In recent years, reports of colistin-resistant Klebsiella pneumoniae (CoRKp) are increasing. However, the molecular mechanism and relevance of colistin resistance and virulence remain unclear. Fourteen CoRKp strains were retrospectively screened from 1884 clinical K. pneumoniae isolates during 2017-2018 in China. Six CoRKp strains belonging to ST11 were MDR strains. Plasmid-mediated mobile colistin-resistance genes had a low prevalence in CoRKp. Our results revealed that up-regulated expression of two-component systems, especially phoPQ, contributed more to colistin resistance. mgrB mutation was the most common molecular mechanism of colistin resistance, caused by either nonsense mutations or insertion sequences, which drove the overexpression of phoPQ system. This study also identified three novel point mutations in pmrAB system, in which D313N mutation in pmrB was proved to increase the MIC to colistin by 16-fold. In addition, 6 out of 14 CoRKP strains independently carried hypervirulence genes. All six strains showed medium-to-high virulence phenotype compared with NTUH-K2044 strain in mice intraperitoneal challenge models. We found that 4 strains were biofilm strong producers and transcriptome analysis revealed that three of them significantly up-regulated expression of type III fimbrial shaft gene mrkA. In conclusion, our result revealed the emergence of colistin-resistant and hypervirulent MDR K. pneumoniae, which is a noticeable superbug and could cause a severe challenge to public health.

Zoonoses, Jan 19, 2023

Human plague, caused by Yersinia pestis, a bacterium which first and foremost occurs in wildlife ... more Human plague, caused by Yersinia pestis, a bacterium which first and foremost occurs in wildlife rodent species but occasionally spills over to people: hence the title "Yersinia pestis and Plague". Plague has brought about three pandemics in history, including the first pandemic Justinian plague (from around 541 CE), the second Black Death (from around 1347 CE), and the third modern plague (from around 1880 CE). Since the etiologic agent for plague was identified by Dr. Alexander Yersin during the third pandemic in Hong Kong of China in 1894 [1], more than 120 years have passed, and we have a better understanding of the physiology, pathogenesis, and evolution of Y. pestis. We have developed technologies for plague diagnosis and treatment. Plague is effectively controlled in most endemic regions, except some parts of Africa. The wide distribution of natural plague foci in Asia, Eurasia, Africa, and the Americas, with occasional occurrences in both rodents and humans or following long-distance travel of plague-infected individuals into large cities reminds us of the threat of a plague outbreak. In this review, we will summarize what we know and what we do not know about plague and its causative agent, Y. pestis. The key issues that need to be resolved are also included (Box).

Emerging Microbes & Infections, 2022

Colistin is regarded as a last-resort agent to combat infections caused by multidrug-resistant (M... more Colistin is regarded as a last-resort agent to combat infections caused by multidrug-resistant (MDR) Gram-negative bacteria, especially carbapenem-resistant isolates. In recent years, reports of colistin-resistant Klebsiella pneumoniae (CoRKp) are increasing. However, the molecular mechanism and relevance of colistin resistance and virulence remain unclear. Fourteen CoRKp strains were retrospectively screened from 1884 clinical K. pneumoniae isolates during 2017-2018 in China. Six CoRKp strains belonging to ST11 were MDR strains. Plasmid-mediated mobile colistin-resistance genes had a low prevalence in CoRKp. Our results revealed that up-regulated expression of two-component systems, especially phoPQ, contributed more to colistin resistance. mgrB mutation was the most common molecular mechanism of colistin resistance, caused by either nonsense mutations or insertion sequences, which drove the overexpression of phoPQ system. This study also identified three novel point mutations in pmrAB system, in which D313N mutation in pmrB was proved to increase the MIC to colistin by 16-fold. In addition, 6 out of 14 CoRKP strains independently carried hypervirulence genes. All six strains showed medium-to-high virulence phenotype compared with NTUH-K2044 strain in mice intraperitoneal challenge models. We found that 4 strains were biofilm strong producers and transcriptome analysis revealed that three of them significantly up-regulated expression of type III fimbrial shaft gene mrkA. In conclusion, our result revealed the emergence of colistin-resistant and hypervirulent MDR K. pneumoniae, which is a noticeable superbug and could cause a severe challenge to public health.