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  • American Society for Microbiology  (6)
  • 1
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 57, No. 4 ( 2013-04), p. 1723-1729
    Abstract: The recent reports of resistance in Plasmodium falciparum to artemisinin derivatives and their partner drugs demand intensive studies toward understanding the molecular mechanisms of resistance. In this study, we examined the in vitro susceptibility of 63 P. falciparum field isolates collected from the China-Myanmar border area to chloroquine (CQ) and piperaquine (PPQ). Parasite isolates remained highly resistant to CQ, with the geometric mean 50% inhibitory concentration (IC 50 ) of 252.7 nM and a range of 51.9 to 1,052.0 nM. In comparison, these parasites had a geometric mean IC 50 of 28.4 nM for PPQ, with a fairly wide range of 5.3 to 132.0 nM, suggesting that certain parasite isolates displayed relatively high levels of resistance to PPQ. Interestingly, within the 4 years of study, the parasites exhibited a continuous decline in susceptibilities to both CQ and PPQ, and there was a significant correlation between responses to CQ and PPQ (Pearson correlation coefficient = 0.79, P 〈 0.0001). Consistent with the CQ-resistant phenotype, all parasites carried the pfcrt K76T mutation, and most parasites had the CVIET type that is prevalent in Southeast Asia. In contrast, pfmdr1 mutations were relatively rare, and no gene amplification was detected. Only the pfmdr1 N1042D mutation was associated with resistance to CQ. For the pfmrp1 gene, four substitutions reached relatively high prevalence of 〉 22%, and the I876V mutation was associated with reduced sensitivity to CQ. However, we could not establish a link between PPQ responses and the polymorphisms in the three genes associated with quinoline drug resistance.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    RVK:
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2013
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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  • 2
    In: Microbiology Spectrum, American Society for Microbiology, Vol. 11, No. 4 ( 2023-08-17)
    Abstract: Influenza A virus (IAV)–methicillin-resistant Staphylococcus aureus (MRSA) coinfection causes severe respiratory infections. The host microbiome plays an important role in respiratory tract infections. However, the relationships among the immune responses, metabolic characteristics, and respiratory microbial characteristics of IAV-MRSA coinfection have not been fully studied. We used specific-pathogen-free (SPF) C57BL/6N mice infected with IAV and MRSA to build a nonlethal model of IAV-MRSA coinfection and characterized the upper respiratory tract (URT) and lower respiratory tract (LRT) microbiomes at 4 and 13 days postinfection by full-length 16S rRNA gene sequencing. Immune response and plasma metabolism profile analyses were performed at 4 days postinfection by flow cytometry and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The relationships among the LRT microbiota, the immune response, and the plasma metabolism profile were analyzed by Spearman’s correlation analysis. IAV-MRSA coinfection showed significant weight loss and lung injury and significantly increased loads of IAV and MRSA in bronchoalveolar lavage fluid (BALF). Microbiome data showed that coinfection significantly increased the relative abundances of Enterococcus faecalis , Enterobacter hormaechei , Citrobacter freundii , and Klebsiella pneumoniae and decreased the relative abundances of Lactobacillus reuteri and Lactobacillus murinus . The percentages of CD4 + /CD8 + T cells and B cells in the spleen; the levels of interleukin-9 (IL-9), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), IL-6, and IL-8 in the lung; and the level of mevalonolactone in plasma were increased in IAV-MRSA-coinfected mice. L. murinus was positively correlated with lung macrophages and natural killer (NK) cells, negatively correlated with spleen B cells and CD4 + /CD8 + T cells, and correlated with multiple plasma metabolites. Future research is needed to clarify whether L. murinus mediates or alters the severity of IAV-MRSA coinfection. IMPORTANCE The respiratory microbiome plays an important role in respiratory tract infections. In this study, we characterized the URT and LRT microbiota, the host immune response, and plasma metabolic profiles during IAV-MRSA coinfection and evaluated their correlations. We observed that IAV-MRSA coinfection induced severe lung injury and dysregulated host immunity and plasma metabolic profiles, as evidenced by the aggravation of lung pathological damage, the reduction of innate immune cells, the strong adaptation of the immune response, and the upregulation of mevalonolactone in plasma. L. murinus was strongly correlated with immune cells and plasma metabolites. Our findings contribute to a better understanding of the role of the host microbiome in respiratory tract infections and identified a key bacterial species, L. murinus , that may provide important references for the development of probiotic therapies.
    Type of Medium: Online Resource
    ISSN: 2165-0497
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2023
    detail.hit.zdb_id: 2807133-5
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  • 3
    In: mSphere, American Society for Microbiology, Vol. 5, No. 4 ( 2020-08-26)
    Abstract: Shigella flexneri is a major cause of bacillary dysentery in Beijing, China. The genetic features and population structure of locally circulating clones remained unclear. In this study, we sequenced the genomes of 93 S. flexneri isolates from patients in Beijing from 2005 to 2018. Phylogenetic analysis revealed a predominant lineage comprised of ST100 isolates that had acquired an extensive repertoire of antimicrobial resistance determinants. A rapid local expansion of the largest clade of this lineage began in 2008 and gradually resulted in the dominance of serotype 2a. Other clades showed substantial evidence of interregional spread from other areas of China. Another lineage consisting of ST18 isolates was also identified and appeared to have persisted locally for nearly 6 decades. These findings suggest that S. flexneri epidemics in Beijing were caused by both local expansion and interregional transmission. IMPORTANCE Beijing is the largest transportation hub in China, with a highly mobile population. Shigella flexneri is a major cause of bacillary dysentery in Beijing. However, little is known about the genetic features and population structure of locally circulating S. flexneri clones. Whole-genome sequencing of 93 S. flexneri isolates revealed that S. flexneri epidemics in Beijing were predominantly caused by an ST100 clone. Interregional spread, rapid local expansion, and acquirement of antimicrobial resistance determinants have cocontributed to the epidemics of this clone. Another ST18 clone was also identified and showed long-term colonization in Beijing. Our study provides comprehensive insights into the population structure and evolutionary history of S. flexneri in Beijing.
    Type of Medium: Online Resource
    ISSN: 2379-5042
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2020
    detail.hit.zdb_id: 2844248-9
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  • 4
    In: Microbiology Spectrum, American Society for Microbiology, Vol. 10, No. 5 ( 2022-10-26)
    Abstract: Water hypoxia (DO  〈  2 mg/L) is a growing global environmental concern that has the potential to significantly influence not only the aquatic ecosystem but also the benthic sedimentary ecosystem. The Changjiang River Estuary hypoxia, classified as one of the world's largest seasonal hypoxic water basins, has been reported to be expanding rapidly in recent decades. However, the microbial community dynamics and responses to this water hypoxia are still unclear. In this study, we examined the abundance, community composition, and distribution of sedimentary archaea, one important component of microbial communities in the Changjiang River Estuary and the East China Sea (ECS). Our results indicated that Thaumarchaeota and Bathyarchaeota were predominant archaeal groups in these research areas, with their 16S rRNA gene abundance ranged from 8.55 × 10 6 to 7.51 × 10 8 and 3.18 × 10 5 to 1.11 × 10 8 copies/g, respectively. The sedimentary archaeal community was mainly influenced by DO, together with the concentration of ammonium, nitrate, and sulfide. In addition, distinct differences in the archaeal community's composition, abundance, and driving factors were discovered between samples from hypoxia and non-hypoxia stations. Furtherly, microbial networks suggest various microbes leading the different activities in hypoxic and normoxic environments. Bathyarchaeota and Thermoprofundales were “key stone” archaeal members of the low-DO network, whereas Thaumarchaeota constituted a significant component of the high-DO network. Our results provide a clear picture of the sedimentary archaeal community in coastal hypoxia zones and indicates potential distinctions of archaea in hypoxia and non-hypoxia environments, including ecological niches and metabolic functions. IMPORTANCE In this study, the sedimentary archaeal community composition and abundance were detailed revealed and quantified based on 16S rRNA genes off the Changjiang River Estuary. We found that the community composition was distinct between hypoxia and non-hypoxia regions, while Thaumarchaeota and Bathyarchaeota dominated in non-hypoxia and hypoxia samples, respectively. In hypoxia regions, the sedimentary archaea were mainly affected by salinity, ammonium, and nitrate, whereas total organic carbon, total nitrogen, and sulfide were major influencing factors in non-hypoxia regions. The distinct microbial network may suggest the niche difference of archaeal community under various oxygen level.
    Type of Medium: Online Resource
    ISSN: 2165-0497
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 2807133-5
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  • 5
    In: Microbiology Spectrum, American Society for Microbiology, Vol. 10, No. 6 ( 2022-12-21)
    Abstract: Klebsiella pneumoniae often causes life-threatening infections in patients globally. Despite its notability, little is known about potential nosocomial outbreak and spread of K. pneumoniae among pediatric patients in low- and middle-income countries. Ninety-eight K. pneumoniae strains isolated from pediatric patients in a large general hospital in China between February 2018 and May 2019 were subjected to nanopore and Illumina sequencing and genomic analysis to elucidate transmission and genetic diversity. The temporal distribution patterns of K. pneumoniae revealed a cluster of sequence type 11 (ST11) strains comprising two clades. Most inferred transmissions were of clade 1, which could be traced to a common ancestor dating to mid-2017. An infant in the coronary care unit played a central role, potentially seeding transmission clusters in other wards. Major genomic changes during the outbreak included chromosomal mutations associated with virulence and gains and losses of plasmids encoding resistance. In summary, we report a nosocomial outbreak among pediatric patients caused by clonal dissemination of KPC-2-producing ST11 K. pneumoniae . Our findings highlight the value of whole-genome sequencing during outbreak investigations and illustrate that transmission chains can be identified during hospital stays. IMPORTANCE We report a nosocomial outbreak among pediatric patients caused by clonal dissemination of bla KPC-2 -carrying ST11 K. pneumoniae . Strains of various sequence types coexist in the complex hospital environment; the quick emergence and spread of ST11 strains were mainly due to the plasmid-mediated acquisition of resistance genes. The spread of hospital infection was highly associated with several specific wards, suggesting the importance of genomic surveillance on wards at high risk of infection.
    Type of Medium: Online Resource
    ISSN: 2165-0497
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 2807133-5
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  • 6
    In: Journal of Virology, American Society for Microbiology, Vol. 97, No. 5 ( 2023-05-31)
    Abstract: Human adenoviruses type 3 (HAdV-3) and type 55 (HAdV-55) are frequently encountered, highly contagious respiratory pathogens with high morbidity rate. In contrast to HAdV-3, one of the most predominant types in children, HAdV-55 is a reemergent pathogen associated with more severe community-acquired pneumonia (CAP) in adults, especially in military camps. However, the infectivity and pathogenicity differences between these viruses remain unknown as in vivo models are not available. Here, we report a novel system utilizing human embryonic stem cells-derived 3-dimensional airway organoids (hAWOs) and alveolar organoids (hALOs) to investigate these two viruses. Firstly, HAdV-55 replicated more robustly than HAdV-3. Secondly, cell tropism analysis in hAWOs and hALOs by immunofluorescence staining revealed that HAdV-55 infected more airway and alveolar stem cells (basal and AT2 cells) than HAdV-3, which may lead to impairment of self-renewal functions post-injury and the loss of cell differentiation in lungs. Additionally, the viral life cycles of HAdV-3 and -55 in organoids were also observed using Transmission Electron Microscopy. This study presents a useful pair of lung organoids for modeling infection and replication differences between respiratory pathogens, illustrating that HAdV-55 has relatively higher replication efficiency and more specific cell tropism in human lung organoids than HAdV-3, which may result in relatively higher pathogenicity and virulence of HAdV-55 in human lungs. The model system is also suitable for evaluating potential antiviral drugs, as demonstrated with cidofovir. IMPORTANCE Human adenovirus (HAdV) infections are a major threat worldwide. HAdV-3 is one of the most predominant respiratory pathogen types found in children. Many clinical studies have reported that HAdV-3 causes less severe disease. In contrast, HAdV-55, a reemergent acute respiratory disease pathogen, is associated with severe community-acquired pneumonia in adults. Currently, no ideal in vivo models are available for studying HAdVs. Therefore, the mechanism of infectivity and pathogenicity differences between human adenoviruses remain unknown. In this study, a useful pair of 3-dimensional (3D) airway organoids (hAWOs) and alveolar organoids (hALOs) were developed to serve as a model. The life cycles of HAdV-3 and HAdV-55 in these human lung organoids were documented for the first time. These 3D organoids harbor different cell types, which are similar to the ones found in humans. This allows for the study of the natural target cells for infection. The finding of differences in replication efficiency and cell tropism between HAdV-55 and -3 may provide insights into the mechanism of clinical pathogenicity differences between these two important HAdV types. Additionally, this study provides a viable and effective in vitro tool for evaluating potential anti-adenoviral treatments.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2023
    detail.hit.zdb_id: 1495529-5
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