BIODEGRADATION
·
2016
·Vol. 27
·期 1
·37-46
·
IF 2.208
Zhou YuYang,Huang Huanlin,Shen Dongsheng
This study evaluated substrate interactions during the aerobic biodegradation of 1, 4-dioxane and BTEX mixtures by a pure culture, Acinetobacter baumannii DD1, which is capable of utilizing 1, 4-dioxane for growth. A. baumannii DD1 could utilize BTEX as a sole carbon source, but could not utilize m -xylene and p -xylene. In binary mixtures, there was a lag of about 14 h before the degradation of BTE, and 1, 4-dioxane only started to be utilized when BTE was completely degraded by 1, 4-dioxane-grown DD1. Furthermore, the biodegradation rate of 1, 4-dioxane decreased from 73.33 to 40.74 mg/(h g dry weight) after the biodegradation of benzene. 1, 4-dioxane could not be degraded after the biodegradation of o -xylene in 80 h. DD1 could also not degrade m -xylene and p -xylene coexisting with 1, 4-dioxane. The ability of DD1 to degrade BTEX occurred in the following order: benzene > ethylbenzene > toluene > o -xylene > m -xylene = p -xylene. The biodegradation of 1, 4-dioxane was not activated in the mixture with o -xylene, primarily because of the accumulation of the specific toxic intermediate, 2, 3-dimethylphenol. The lag in BTE degradation was presumably because of the induction of enzymes necessary for BTE degradation. Additionally, SDS-PAGE analysis demonstrated that there were different proteins during the degradation of benzene and 1, 4-dioxane.
研究领域:
环境微生物学
·
生物修复
·
生物化学
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DOI
PubMed
高影响因子
STRUCTURE
·
2025
·
IF 4.3
Zhenlin Ouyang,Wenbo He,Di Wu,Hao An,Lei Duan,Min Jiao,Xiaoyu He,Qinyue Yu,Jiaxin Zhang,Qian Qin,Ruochen Wang,Fang Zheng,Peter M. Hwang,Xiaoting Hua,Li Zhu,Yurong Wen
Multidrug-resistant Acinetobacter baumannii has emerged as one of the most antibiotic-resistant bacterial pathogens associated with nosocomial infection, with its resistance highly depending on multiple multidrug efflux pumps. Here, we report the cryoelectron microscopy (cryo-EM) structure of Acinetobacter drug efflux G (AdeG), the inner membrane component of one of three important resistance-nodulation-cell division (RND) pump family members in A. baumannii , which is involved in drug resistance to chloramphenicol, trimethoprim, ciprofloxacin, and clindamycin. We systematically compare the structures and substrate binding specificities of AdeG, AdeB, and AdeJ multidrug efflux pumps via molecular docking, revealing potential determinants for drug binding. Knockout experiments demonstrate a functional complementarity between AdeABC, AdeFGH, and AdeIJK. Our study provides a structural understanding of A. baumannii multidrug efflux pump AdeG and reveals complementary drug efflux activity between AdeG and other RND efflux pumps, which may promote further rational drug discovery efforts targeting multidrug efflux pumps.
研究领域:
微生物学
·
结构生物学
·
药理学
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DOI
PubMed
高影响因子
AICHE JOURNAL
·
2026
·
IF 4.4
Pei Qiao,Yi Guo,Yanan Liu,Chenghua Zhu,Di Cheng,Youshan Zhou,Panpan Song
Phthalate esters (PAEs) are pervasive environmental pollutants that require efficient biodegradation. The substrate specificity of PAEs-degrading microorganisms hinges critically on the catalytic selectivity of microbial esterases. To elucidate the molecular basis of the specificity of Type III PAEs esterases, we developed a chromogenic assay and further integrated machine learning-driven enzyme mining with functional characterization and molecular dynamics analysis. A novel microorganism, Acinetobacter sp. DY-1, was isolated with diverse PAEs-degrading capacities. The esterase 1952 from strain DY-1 exhibited broad substrate specificity and high catalytic efficiency, with a marked preference for long-chain PAEs, such as DEHP. Molecular dynamics simulations revealed stable hydrophobic interactions underpinning 1952s affinity for DEHP. Through targeted mutagenesis, we identified key residues (Leu64, Leu68, and His229) that are essential for substrate binding and catalysis. Their substitution with polar residues drastically reduced DEHP degradation, while the G178Y mutant enhanced activity via π-stacking interactions. This study deciphers the structural determinants of PAE esterase specificity, enabling precise enzyme engineering.
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高影响因子
MICROBIOLOGICAL RESEARCH
·
2021
·
IF 5.415
Huanhuan Li,Xinyang Du,Chaoyi Chen,Jiangfeng Qi,Ying Wang
As a major secondary metabolite derived from a dominant marine filamentous fungus A7, kojic acid might confer the strain a competitive advantage in natural colonization. The bioactivities of kojic acid against bacterial growth and biofilm formation were investigated against Acinetobacter baumannii ( A. baumannii ) ATCC 19606. Then, transcriptomics and metabolomics were integrated to characterize the underlying mechanisms. It turned out that kojic acid exhibited a significantly suppressive impact against biofilm but a weak bacteriostatic activity. Meanwhile, a variety of transcriptional and metabolomic profiles were altered within biofilm formation as a result of kojic acid exposure. The alterations highlighted the mechanisms underlying biofilm formation, comprising of quorum sensing, fimbria assembly, bacterial virulence and metabolic plasticity, which could somewhat be hampered by kojic acid. The present study comprehensively elucidated multifactorial schemes for kojic acid combating biofilm formation of A. baumannii , which might provide mechanistic insights into the development of therapeutic strategies against this notorious pathogen. Meanwhile, our observations might shed new light on the ecological roles of kojic acid, e.g. , serving as chemical deterrents for host adaptation to marine niches, which, however, awaits further validation.
研究领域:
微生物学
·
药理学
·
分子生物学
·
海洋生物学
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DOI
PubMed
高影响因子
Catalysis Science & Technology
·
2021
·Vol. 11
·期 12
·4208-4215
·
IF 6.119
Liuzhu Wang,Shiqing Diao,Yangyang Sun,Shuiqin Jiang,Yan Liu,Hualei Wang,Dongzhi Wei
L-Homoalanine, a useful building block for the synthesis of several chiral drugs, is generally synthesized through biocascades using natural amino acids as cheap starting reactants. However, the addition of expensive external cofactors and the low efficiency of leucine dehydrogenases towards the intermediate 2-ketobutyric acid are two major challenges in industrial applications. Herein, a dual cofactor-dependent glutamate dehydrogenase from Acinetobacter tandoii (AtGluDH) was identified to help make full use of the intracellular pool of cofactors when using whole-cell catalysis. Through reconstruction of the hydrophobic network between the enzyme and the terminal methyl group of the substrate 2-ketobutyric acid, the strict substrate specificity of AtGluDH towards α-ketoglutarate was successfully changed, and the activity obtained by the most effective mutant (K76L/T180C) was 17.2 times higher than that of the wild-type protein. A three-enzyme co-expression system was successfully constructed in order to help release the mass transfer restriction. Using 1 M L-threonine, which is close to the solubility limit, we obtained a 99.9% yield of L-homoalanine in only 3.5 h without adding external coenzymes to the cascade, giving 99.9% ee and a 29.2 g L−1 h−1 space–time yield. Additionally, the activities of the engineered AtGluDH towards some other hydrophobic amino acids were also improved to 1.1–11.2 fold. Therefore, the engineering design of some dual cofactor-dependent GluDHs could not only eliminate the low catalytic activity of unnatural substrates but also enhance the cofactor utilization efficiency of these enzymes in industrial applications.
研究领域:
生物化学
·
生物技术
·
酶工程
·
有机化学
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DOI
高影响因子
Nanoscale
·
2020
·Vol. 12
·期 26
·13948-13957
·
IF 6.895
Wenzhen Liu,Yuxiang Zhang,Wenwu You,Jianqiang Su,Shaohua Yu,Tao Dai,Yunmei Huang,Xueyuan Chen,Xiaorong Song,Zhuo Chen
Extensively drug-resistant Acinetobacter baumannii (XDR-AB) has raised considerable concerns due to its mortal damage to humans and its high transmission rate of infections in hospitals. However, current antibiotics not only show poor anti-infection effects in vivo but also frequently cause high nephrotoxicity and neurotoxicity. Herein, we report a near-infrared (NIR) light-initiated antimicrobial photodynamic therapy (aPDT) to effectively treat in vivo XDR-AB infections based on photosensitizer (PS) loaded upconversion nanoparticles (UCNPs, LiYF4:Yb/Er). Such nanoagents feature robust NIR triggered UC luminescence and high-efficiency energy transfer from UCNPs to the loaded PS, thereby allowing NIR-triggered generation of reactive oxygen species (ROS) for destroying the bacterial cell membrane. This strategy permits a high antibacterial activity against XDR-AB, resulting in a decline of 4.72 log10 in viability at a dose of 50 μg mL−1 UCNPs-PVP-RB with 980 nm laser irradiation (1 W cm−2). More significantly, we can achieve excellent therapeutic efficacy against deep-tissue (about 5 mm) XDR-AB infections without causing any side effects in the murine model. In brief, such NIR-activated aPDT may open up new avenues for treating various deep-tissue intractable infections.
研究领域:
纳米技术
·
光动力疗法
·
抗菌剂
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 18
·6738
·
IF 4.6
Shuanghu Fan,Jingjing Guo,Shaoyan Han,Haina Du,Zimeng Wang,Yajuan Fu,Hui Han,Xiaoqiang Hou,Weixuan Wang
Phthalic acid esters (PAEs), which are widespread environmental contaminants, can be efficiently biodegraded, mediated by enzymes such as hydrolases. Despite great advances in the characterization of PAE hydrolases, which are the most important enzymes in the process of PAE degradation, their molecular catalytic mechanism has rarely been systematically investigated.Acinetobactersp. LUNF3, which was isolated from contaminated soil in this study, demonstrated excellent PAE degradation at 30 °C and pH 5.0–11.0. After sequencing and annotating the complete genome, the genedphAN1, encoding a novel putative PAE hydrolase, was identified with the conserved motifs catalytic triad (Ser201-Asp295-His325) and oxyanion hole (H127GGG130). DphAN1 can hydrolyze DEP (diethyl phthalate), DBP (dibutyl phthalate) and BBP (benzyl butyl phthalate). The high activity of DphAN1 was observed under a wide range of temperature (10–40 °C) and pH (6.0–9.0). Moreover, the metal ions (Fe2+, Mn2+, Cr2+and Fe3+) and surfactant TritonX-100 significantly activated DphAN1, indicating a high adaptability and tolerance of DphAN1 to these chemicals. Molecular docking revealed the catalytic triad, oxyanion hole and other residues involved in binding DBP. The mutation of these residues reduced the activity of DphAN1, confirming their interaction with DBP. These results shed light on the catalytic mechanism of DphAN1 and may contribute to protein structural modification to improve catalytic efficiency in environment remediation.Keywords:Acinetobacter;biodegradation;genome sequencing;HSL family hydrolase;site-directed mutagenesis
研究领域:
环境科学
·
微生物学
·
分子生物学
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DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2023
·
IF 5.2
Xinyi Zhong,Kai Deng,Xiuhan Yang,Xu Song,Yuanfeng Zou,Xun Zhou,Huaqiao Tang,Lixia Li,Yuping Fu,Zhongqiong Yin,Hongping Wan,Xinghong Zhao
The antibiotic resistance of Acinetobacter baumannii poses a significant threat to global public health, especially those strains that are resistant to carbapenems. Therefore, novel strategies are desperately needed for the treatment of infections caused by antibiotic-resistant A. baumannii . In this study, we report that brevicidine, a bacterial non-ribosomally produced cyclic lipopeptide, shows synergistic effects with multiple outer membrane-impermeable conventional antibiotics against A. baumannii . In particular, brevicidine, at a concentration of 1 μM, lowered the minimum inhibitory concentration of erythromycin, azithromycin, and rifampicin against A. baumannii strains by 32–128-fold. Furthermore, mechanistic studies were performed by employing erythromycin as an example of an outer membrane-impermeable conventional antibiotic, which showed the best synergistic effects with brevicidine against the tested A. baumannii strains in the present study. The results demonstrate that brevicidine disrupted the outer membrane of A. baumannii at a concentration range of 0.125–4 μM in a dose-dependent manner. This capacity of brevicidine could help the tested outer membrane-impermeable antibiotics enter A. baumannii cells and thereafter exert their antimicrobial activity. In addition, the results show that brevicidine–erythromycin combination exerted strong A. baumannii killing capacity by the enhanced inhibition of adenosine triphosphate biosynthesis and accumulation of reactive oxygen species, which are the main mechanisms causing the death of bacteria. Interestingly, brevicidine and erythromycin combination showed good therapeutic effects on A. baumannii -induced mouse peritonitis–sepsis models. These findings demonstrate that brevicidine is a promising sensitizer candidate of outer membrane-impermeable conventional antibiotics for treating A. baumannii infections in the post-antibiotic age.
研究领域:
微生物学
·
药理学
·
传染病学
·
生物医学研究
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL RESEARCH
·
2021
·
IF 6.498
Zhi-Ling Li,Di Cao,Cai-Hua Bai,Xiao-Jing Yao,Xiao-Qiu Lin,Si-Pei Wang,Jun Nan,Bin Liang,Li-Wei Li,Kai Sun,Ai-Jie Wang
The response of the denitrification community to long-term antibiotic exposure requires further investigation. Here, the significantly altered denitrifying community structure and function were observed by continuous exposure to 1 mg/L sulfamethoxazole (SMZ) or chlortetracycline (CTC) for 180 d in the expanded granular sludge bed reactors. Thaurea , positively correlated with SMZ and NO 3 − removal efficiency ( NrE ), was highly enriched in the SMZ-added reactor, while, Comamons and Acinetobacter were largely inhibited. The acute inhibited and then gradual-recovered NrE (87.17–90.38 %) was observed with highly expressed narG , indicating the adaptability of Thaurea to SMZ. However, the abundance of Thaurea and Comamonas greatly decreased, while Melioribacter and Acinetobacter were largely enriched in the CTC-added reactor. CTC created more serious and continuous inhibition of NO 3 − reduction ( NrE of 64.53–66.95 %), with lowly expressed narG . Improved NO 2 − reduction capacity was observed in both reactors (70.16–95.42 %) with highly expressed nirS and nosZ , revealing the adaptability of NO 2 − reduction populations to antibiotics.
研究领域:
环境微生物学
·
生物技术
·
污水处理
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Xisheng Li,Rong Gui,Jian Li,Rong Huang,Yinghui Shang,Qiangqiang Zhao,Haiting Liu,Haiye Jiang,Xueling Shang,Xin Wu,Xinmin Nie
In the face of the abundant production of various types of carbapenemases, the antibacterial efficiency of imipenem, seen as “the last line of defense”, is weakening. Following, the incidence of carbapenem-resistant Acinetobacter baumannii (CRAB), which can generate antibiotic-resistant biofilms, is increasing. Based on the superior antimicrobial activity of silver nanoparticles against multifarious bacterial strains compared with common antibiotics, we constructed the IPM@AgNPs-PEG-NOTA nanocomposite (silver nanoparticles were coated with SH-PEG-NOTA as well as loaded by imipenem) whose core was a silver nanoparticle to address the current challenge, and IPM@AgNPs-PEG-NOTA was able to function as a novel smart pH-sensitive nanodrug system. Synergistic bactericidal effects of silver nanoparticles and imipenem as well as drug-resistance reversal via protection of the β-ring of carbapenem due to AgNPs-PEG-NOTA were observed; thus, this nanocomposite confers multiple advantages for efficient antibacterial activity. Additionally, IPM@AgNPs-PEG-NOTA not only offers immune regulation and accelerates tissue repair to improve therapeutic efficacy in vivo but also can prevent the interaction of pathogens and hosts. Compared with free imipenem or silver nanoparticles, this platform significantly enhanced antibacterial efficiency while increasing reactive oxygen species (ROS) production and membrane damage, as well as affecting cell wall formation and metabolic pathways. According to the results of crystal violet staining, LIVE/DEAD backlight bacterial viability staining, and real-time quantitative polymerase chain reaction (RT-qPCR), this silver nanocomposite downregulated the levels of ompA expression to prevent formation of biofilms. In summary, this research demonstrated that the IPM@AgNPs-PEG-NOTA nanocomposite is a promising antibacterial agent of security, pH sensitivity, and high efficiency in reversing resistance and synergistically combatting carbapenem-resistant A. baumannii. In the future, various embellishments and selected loads for silver nanoparticles will be the focus of research in the domains of medicine and nanotechnology.
研究领域:
纳米技术
·
抗菌剂
·
药学
·
微生物学
·
材料科学
·
生物医学工程
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DOI
PubMed
高影响因子
Heliyon
·
2023
·Vol. 9
·期 11
·e21871
·
IF 4
Tianhang Chen,Haixia Du,Huifen Zhou,Yu He,Jiehong Yang,Chang Li,Chenxing Wei,Daojun Yu,Haitong Wan
Yinhuapinggan granule (YHPG) is a traditional Chinese medicine prescription with rich clinical experience for the treatment of colds and coughs. The aim of this study is to investigate the protective effect of YHPG on multidrug-resistant (MDR) Acinetobacter baumannii ( A. baumannii ) infection in vivo and its potential anti-inflammatory mechanism. BALB/c mice were intranasally inoculated with MDR A. baumannii strain to establish the pneumonia infection model, and received intraperitoneally cyclophosphamide to form immunosuppression before attack. YHPG (6, 12 and 18 g/kg) was administered by gavage once a day for 3 consecutive days after infection. The protective effect of YHPG was evaluated by lung index, spleen index, thymus index, pathological changes of lung tissue and inflammatory factors (IL-1β, IL-6 and TNF-α) in serum. The expression of key targets of NF-κB/NLRP3 signaling pathway in vivo was analyzed by immunohistochemistry, immunofluorescence, reverse transcription quantitative PCR (RT-qPCR) and Western blot. The results showed that YHPG improved the lung index and its inhibition rate, immune organ indexes and lung pathological changes in infected mice, and significantly reduced IL-1β, IL-6 and TNF-α levels in serum. In addition, YHPG significantly down-regulated the mRNA and protein expression of NF-κB p65, NLRP3, ASC, Caspase-1, TNF-α, IL-6 and IL-1β in mice lung tissue. The results of the current study demonstrated that YHPG has significant protective effects on mice infected with MDR A.baumannii , which may be related to the regulation of inflammatory factors and NF-κB/NLRP3 signaling pathway, indicating that YHPG has a wide range of clinical application value and provides a theoretical basis for its treatment of MDR A.baumannii infection.
研究领域:
中药学
·
免疫学
·
感染性疾病研究
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DOI
PubMed
高影响因子
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
·
2018
·Vol. 62
·期 2
·
IF 4.256
Cheng Wang,Gaomei Zhao,Song Wang,Yin Chen,Yali Gong,Shilei Chen,Yang Xu,Mengjia Hu,Xinmiao Wang,Hao Zeng,Aiping Wang,Dengqun Liu,Yongping Su,Tianmin Cheng,Fang Chen,Junping Wang
The increasing incidence of multidrug-resistant Acinetobacter baumannii (MDRAb) infections worldwide has necessitated the development of novel antibiotics. Human defensin 5 (HD5) is an endogenous peptide with a complex architecture and antibacterial activity against MDRAb. In the present study, we attempted to simplify the structure of HD5 by removing disulfide bonds. We found that the Cys2-4 bond was most indispensable for HD5 to inactivate MDRAb, although the antibacterial activity of the derivative was significantly attenuated. We then replaced the noncationic and nonhydrophobic residues with electropositive Arg to increase the antibacterial activity of HD5 derivative that contains a Cys2-4 bond, obtaining another derivative termed HD5d5. The in vitro antibacterial assay and irradiation-wound-infection animal experiment both showed that HD5d5 was much more effective than HD5 at eliminating MDRAb. Further investigations revealed that HD5d5 efficiently bound to outer membrane lipid A and penetrated membranes, leading to bacterial collapse and peptide translocation. Compared to HD5, more HD5d5 molecules were located in the cytoplasm of MDRAb, and HD5d5 was more efficient at reducing the activities of superoxide dismutase and catalase, causing the accumulation of reactive oxygen species that are detrimental to microbes. In addition, HD5 failed to suppress the pathogenic outer membrane protein A of Acinetobacter baumannii (AbOmpA) at concentrations up to 50 μg/ml, whereas HD5d5 strongly bound to AbOmpA and exhibited a dramatic toxin-neutralizing ability, thus expanding the repertoire of drugs that is available to treat MDRAb infections.
研究领域:
微生物学
·
药理学
·
传染病学
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产品关联
DOI
PubMed
高影响因子
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