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  • 1
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    Online Resource
    Activity of Imipenem-Relebactam against a Large Collection of Pseudomonas aeruginosa Clinical Isolates and Isogenic β-Lactam-Resistant Mutants
    American Society for Microbiology ; 2020
    In:  Antimicrobial Agents and Chemotherapy Vol. 64, No. 2 ( 2020-01-27)
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 64, No. 2 ( 2020-01-27)
    Abstract: Imipenem and imipenem-relebactam MICs were determined for 1,445 Pseudomonas aeruginosa clinical isolates and a large panel of isogenic mutants showing the most relevant mutation-driven β-lactam resistance mechanisms. Imipenem-relebactam showed the highest susceptibility rate (97.3%), followed by colistin and ceftolozane-tazobactam (both 94.6%). Imipenem-relebactam MICs remained ≤2 μg/ml in all 16 isogenic PAO1 mutants and in 8 pairs of extensively drug-resistant clinical strains that had developed resistance to ceftolozane-tazobactam and ceftazidime-avibactam due to mutations in OXA-10 or AmpC.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.02165-19
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2020
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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  • 2
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    Widespread Detection of Yersiniabactin Gene Cluster and Its Encoding Integrative Conjugative Elements (ICE Kp ) among Nonoutbreak OXA-48-Producing Klebsiella pneumoniae Clinical Isolates from Spain and the Netherlands
    American Society for Microbiology ; 2023
    In:  Microbiology Spectrum Vol. 11, No. 4 ( 2023-08-17)
    Details
    In: Microbiology Spectrum, American Society for Microbiology, Vol. 11, No. 4 ( 2023-08-17)
    Abstract: In this study, we determined the presence of virulence factors in nonoutbreak, high-risk clones and other isolates belonging to less common sequence types associated with the spread of OXA-48-producing Klebsiella pneumoniae clinical isolates from The Netherlands ( n  = 61) and Spain ( n  = 53). Most isolates shared a chromosomally encoded core of virulence factors, including the enterobactin gene cluster, fimbrial fim and mrk gene clusters, and urea metabolism genes ( ureAD ). We observed a high diversity of K-Locus and K/O loci combinations, KL17 and KL24 (both 16%), and the O1/O2v1 locus (51%) being the most prevalent in our study. The most prevalent accessory virulence factor was the yersiniabactin gene cluster (66.7%). We found seven yersiniabactin lineages— ybt  9, ybt  10, ybt  13, ybt  14, ybt  16, ybt  17, and ybt  27—which were chromosomally embedded in seven integrative conjugative elements (ICE Kp ): ICE Kp3 , ICE Kp4 , ICE Kp2 , ICE Kp5 , ICE Kp12 , ICE Kp10 , and ICE Kp22 , respectively. Multidrug-resistant lineages—ST11, ST101, and ST405—were associated with ybt  10/ICE Kp4 , ybt  9/ICE Kp3 , and ybt  27/ICE Kp22 , respectively. The fimbrial adhesin kpi operon ( kpiABCDEFG ) was predominant among ST14, ST15, and ST405 isolates, as well as the ferric uptake system kfuABC , which was also predominant among ST101 isolates. No convergence of hypervirulence and resistance was observed in this collection of OXA-48-producing K. pneumoniae clinical isolates. Nevertheless, two isolates, ST133 and ST792, were positive for the genotoxin colibactin gene cluster (ICE Kp10 ). In this study, the integrative conjugative element, ICE Kp , was the major vehicle for yersiniabactin and colibactin gene clusters spreading. IMPORTANCE Convergence of multidrug resistance and hypervirulence in Klebsiella pneumoniae isolates has been reported mostly related to sporadic cases or small outbreaks. Nevertheless, little is known about the real prevalence of carbapenem-resistant hypervirulent K. pneumoniae since these two phenomena are often separately studied. In this study, we gathered information on the virulent content of nonoutbreak, high-risk clones (i.e., ST11, ST15, and ST405) and other less common STs associated with the spread of OXA-48-producing K. pneumoniae clinical isolates. The study of virulence content in nonoutbreak isolates can help us to expand information on the genomic landscape of virulence factors in K. pneumoniae population by identifying virulence markers and their mechanisms of spread. Surveillance should focus not only on antimicrobial resistance but also on virulence characteristics to avoid the spread of multidrug and (hyper)virulent K. pneumoniae that may cause untreatable and more severe infections.
    Type of Medium: Online Resource
    ISSN: 2165-0497
    URL: Article
    DOI: 10.1128/spectrum.04716-22
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2023
    detail.hit.zdb_id: 2807133-5
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  • 3
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    Inactivated Vaccine-Induced SARS-CoV-2 Variant-Specific Immunity in Children
    American Society for Microbiology ; 2022
    In:  mBio Vol. 13, No. 6 ( 2022-12-20)
    Details
    In: mBio, American Society for Microbiology, Vol. 13, No. 6 ( 2022-12-20)
    Abstract: Multiple vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been evaluated in clinical trials. However, trials addressing the immune response in the pediatric population are scarce. The inactivated vaccine CoronaVac has been shown to be safe and immunogenic in a phase 1/2 clinical trial in a pediatric cohort in China. Here, we report interim safety and immunogenicity results of a phase 3 clinical trial for CoronaVac in healthy children and adolescents in Chile. Participants 3 to 17 years old received two doses of CoronaVac in a 4-week interval until 31 December 2021. Local and systemic adverse reactions were registered for volunteers who received one or two doses of CoronaVac. Whole-blood samples were collected from a subgroup of 148 participants for humoral and cellular immunity analyses. The main adverse reaction reported after the first and second doses was pain at the injection site. Four weeks after the second dose, an increase in neutralizing antibody titer was observed in subjects relative to their baseline visit. Similar results were found for activation of specific CD4 + T cells. Neutralizing antibodies were identified against the Delta and Omicron variants. However, these titers were lower than those for the D614G strain. Importantly, comparable CD4 + T cell responses were detected against these variants of concern. Therefore, CoronaVac is safe and immunogenic in subjects 3 to 17 years old, inducing neutralizing antibody secretion and activating CD4 + T cells against SARS-CoV-2 and its variants. (This study has been registered at ClinicalTrials.gov under no. NCT04992260.) IMPORTANCE This work evaluated the immune response induced by two doses of CoronaVac separated by 4 weeks in healthy children and adolescents in Chile. To date, few studies have described the effects of CoronaVac in the pediatric population. Therefore, it is essential to generate knowledge regarding the protection of vaccines in this population. Along these lines, we reported the anti-S humoral response and cellular immune response to several SARS-CoV-2 proteins that have been published and recently studied. Here, we show that a vaccination schedule consisting of two doses separated by 4 weeks induces the secretion of neutralizing antibodies against SARS-CoV-2. Furthermore, CoronaVac induces the activation of CD4 + T cells upon stimulation with peptides from the proteome of SARS-CoV-2. These results indicate that, even though the neutralizing antibody response induced by vaccination decreases against the Delta and Omicron variants, the cellular response against these variants is comparable to the response against the ancestral strain D614G, even being significantly higher against Omicron.
    Type of Medium: Online Resource
    ISSN: 2150-7511
    URL: Article
    DOI: 10.1128/mbio.01311-22
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 2557172-2
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  • 4
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    Efficacy and Safety of Oral Fosfomycin for Asymptomatic Bacteriuria in Kidney Transplant Recipients: Results from a Spanish Multicenter Cohort
    American Society for Microbiology ; 2021
    In:  Antimicrobial Agents and Chemotherapy Vol. 65, No. 5 ( 2021-04-19)
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 65, No. 5 ( 2021-04-19)
    Abstract: Current guidelines recommend against systematic screening for or treating asymptomatic bacteriuria (AB) among kidney transplant (KT) recipients, although the evidence regarding episodes occurring early after transplantation or in the presence of anatomical abnormalities is inconclusive. Oral fosfomycin may constitute a good option for the treatment of posttransplant AB, particularly due to the emergence of multidrug-resistant (MDR) uropathogens. Available clinical evidence supporting its use in this specific setting, however, remains scarce. We performed a retrospective study in 14 Spanish institutions from January 2005 to December 2017. Overall, 137 episodes of AB diagnosed in 133 KT recipients treated with oral fosfomycin (calcium and trometamol salts) with a test-of-cure urine culture within the first 30 days were included. Median time from transplantation to diagnosis was 3.1 months (interquartile range [IQR], 1.1 to 10.5). Most episodes (96.4% [132/137] ) were caused by Gram-negative bacteria (GNB), and 56.9% (78/137) were categorized as MDR (extended‐spectrum β‐lactamase‐producing Enterobacterales [20.4%] and carbapenem‐resistant GNB [2.9%] ). Rate of microbiological failure at month 1 was 40.1% (95% confidence interval [CI], 31.9% to 48.9%) for the whole cohort and 42.3% (95% CI, 31.2% to 54.0%) for episodes due to MDR pathogens. Previous urinary tract infection (odds ratio [OR] , 2.42; 95% CI, 1.11 to 5.29; P value = 0.027) and use of fosfomycin as salvage therapy (OR, 8.31; 95% CI, 1.67 to 41.35; P value = 0.010) were predictors of microbiological failure. No severe treatment-related adverse events were detected. Oral fosfomycin appears to be a suitable and safe alternative for the treatment (if indicated) of AB after KT, including those episodes due to MDR uropathogens.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.02267-20
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2021
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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  • 5
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    A Parasite Biomarker Set for Evaluating Benznidazole Treatment Efficacy in Patients with Chronic Asymptomatic Trypanosoma cruzi Infection
    American Society for Microbiology ; 2019
    In:  Antimicrobial Agents and Chemotherapy Vol. 63, No. 10 ( 2019-10)
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 63, No. 10 ( 2019-10)
    Abstract: One of the current greatest challenges of Chagas disease is the establishment of biomarkers to assess the efficacy of drugs in a short period of time. In this context, the reactivity of sera from 66 adults with chronic indeterminate Chagas disease (IND) for a set of four Trypanosoma cruzi antigens (KMP11, PFR2, HSP70, and 3973 d ) was analyzed before and after benznidazole treatment. The results showed that the reactivity against these antigens decreased at 9, 24, and 48 months after treatment. Moreover, the 42.4% and 68.75% of IND patients met the established standard criteria of therapeutic efficacy (STEC) at 24 and 48 months posttreatment, respectively. Meeting the STEC implied that there was a continuous decrease in the reactivity of the patient sera against the four antigens after treatment and that there was a substantial decrease in the reactivity for at least two of the antigens. This important decrease in reactivity may be associated with a drastic reduction in the parasite load, but it is not necessarily associated with a parasitological cure. After treatment, a positive PCR result was only obtained in patients who did not meet the STEC. The percentage of granzyme B + /perforin + CD8 + T cells was significantly higher in patients who met the STEC than in those who did not meet the STEC (35.2% versus 2.2%; P   〈  0.05). Furthermore, the patients who met the STEC exhibited an increased quality of the multifunctional response of the antigen-specific CD8 + T cells compared with that in the patients who did not meet the STEC.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.02436-18
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2019
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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  • 6
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    Efficacy of Rifampin and Its Combinations with Imipenem, Sulbactam, and Colistin in Experimental Models of Infection Caused by Imipenem-Resistant Acinetobacter baumannii
    American Society for Microbiology ; 2010
    In:  Antimicrobial Agents and Chemotherapy Vol. 54, No. 3 ( 2010-03), p. 1165-1172
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 54, No. 3 ( 2010-03), p. 1165-1172
    Abstract: There are currently no defined optimal therapies available for multidrug-resistant (MDR) Acinetobacter baumannii infections. We evaluated the efficacy of rifampin, imipenem, sulbactam, colistin, and their combinations against MDR A. baumannii in experimental pneumonia and meningitis models. The bactericidal in vitro activities of rifampin, imipenem, sulbactam, colistin, and their combinations were tested using time-kill curves. Murine pneumonia and rabbit meningitis models were evaluated using the A. baummnnii strain Ab1327 (with MICs for rifampin, imipenem, sulbactam, and colistin of 4, 32, 32, and 0.5 mg/liter, respectively). Mice were treated with the four antimicrobials and their combinations. For the meningitis model, the efficacies of colistin, rifampin and its combinations with imipenem, sulbactam, or colistin, and of imipenem plus sulbactam were assayed. In the pneumonia model, compared to the control group, (i) rifampin alone, (ii) rifampin along with imipenem, sulbactam, or colistin, (iii) colistin, or (iv) imipenem plus sulbactam significantly reduced lung bacterial concentrations (10.6 ± 0.27 [controls] versus 3.05 ± 1.91, 2.07 ± 1.82, 2.41 ± 1.37, 3.4 ± 3.07, 6.82 ± 3.4, and 4.22 ± 2.72 log 10 CFU/g, respectively [means ± standard deviations]), increased sterile blood cultures (0% versus 78.6%, 100%, 93.3%, 93.8%, 73.3%, and 50%), and improved survi val (0% versus 71.4%, 60%, 46.7%, 43.8%, 40%, and 85.7%). In the meningitis model rifampin alone or rifampin plus colistin reduced cerebrospinal fluid bacterial counts (−2.6 and −4.4 log 10 CFU/ml). Rifampin in monotherapy or with imipenem, sulbactam, or colistin showed efficacy against MDR A. baumannii in experimental models of pneumonia and meningitis. Imipenem or sulbactam may be appropriate for combined treatment when using rifampin.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.00367-09
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2010
    detail.hit.zdb_id: 1496156-8
    SSG: 12
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  • 7
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    Draft Genome Sequences of Sporulation-Impaired Bacillus pumilus Strain NRS576 and Its Native Plasmid p576
    American Society for Microbiology ; 2019
    In:  Microbiology Resource Announcements Vol. 8, No. 16 ( 2019-04-18)
    Details
    In: Microbiology Resource Announcements, American Society for Microbiology, Vol. 8, No. 16 ( 2019-04-18)
    Abstract: Bacillus pumilus spores can cause foodborne poisonings. B. pumilus strain NRS576 forms spores with a very reduced efficiency due to the presence of a plasmid, named p576. Here, we report the genome sequence of strain B. pumilus NRS576 and its plasmid p576.
    Type of Medium: Online Resource
    ISSN: 2576-098X
    URL: Article
    DOI: 10.1128/MRA.00089-19
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2019
    detail.hit.zdb_id: 2968655-6
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  • 8
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    Draft Genome Sequences of Two Streptococcus pneumoniae Strains Causing Invasive Infections in Children in Qatar
    American Society for Microbiology ; 2019
    In:  Microbiology Resource Announcements Vol. 8, No. 23 ( 2019-06-06)
    Details
    In: Microbiology Resource Announcements, American Society for Microbiology, Vol. 8, No. 23 ( 2019-06-06)
    Abstract: Invasive pneumococcal infections are a major cause of morbidity and mortality in the pediatric population. We report the draft genomes of two clinical Streptococcus pneumoniae isolates associated with severe infections in children in Qatar. The genome statistics are described, along with the strain types and serotypes predicted from the assembled genomes.
    Type of Medium: Online Resource
    ISSN: 2576-098X
    URL: Article
    DOI: 10.1128/MRA.00511-19
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2019
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  • 9
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    Selection of AmpC β-Lactamase Variants and Metallo-β-Lactamases Leading to Ceftolozane/Tazobactam and Ceftazidime/Avibactam Resistance during Treatment of MDR/XDR Pseudomonas aeruginosa Infections
    American Society for Microbiology ; 2022
    In:  Antimicrobial Agents and Chemotherapy Vol. 66, No. 2 ( 2022-02-15)
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 66, No. 2 ( 2022-02-15)
    Abstract: Infections caused by ceftolozane-tazobactam and ceftazidime-avibactam-resistant P. aeruginosa infections are an emerging concern. We aimed to analyze the underlying ceftolozane-tazobactam and ceftazidime-avibactam resistance mechanisms in all multidrug-resistant or extensively drug-resistant (MDR/XDR) P. aeruginosa isolates recovered during 1 year (2020) from patients with a documented P. aeruginosa infection. Fifteen isolates showing ceftolozane-tazobactam and ceftazidime-avibactam resistance were evaluated. Clinical conditions, previous positive cultures, and β-lactams received in the previous month were reviewed for each patient. MICs were determined by broth microdilution. Multilocus sequence types (MLSTs) and resistance mechanisms were determined using short- and long-read whole-genome sequencing (WGS). The impact of Pseudomonas - derived cephalosporinases (PDCs) on β-lactam resistance was demonstrated by cloning into an ampC -deficient PAO1 derivative (PAOΔC) and construction of 3D models. Genetic support of acquired β-lactamases was determined in silico from high-quality hybrid assemblies. In most cases, the isolates were recovered after treatment with ceftolozane-tazobactam or ceftazidime-avibactam. Seven isolates from different sequence types (STs) owed their β-lactam resistance to chromosomal mutations and all displayed specific substitutions in PDC: Phe121Leu and Gly222Ser, Pro154Leu, Ala201Thr, Gly214Arg, ΔGly203-Glu219, and Glu219Lys. In the other eight isolates, the ST175 clone was overrepresented (6 isolates) and associated with IMP-28 and IMP-13, whereas two ST1284 isolates produced VIM-2. The cloned PDCs conferred enhanced cephalosporin resistance. The 3D PDC models revealed rearrangements affecting residues involved in cephalosporin hydrolysis. Carbapenemases were chromosomal (VIM-2) or plasmid-borne (IMP-28, IMP-13) and associated with class-1 integrons located in Tn402-like transposition modules. Our findings highlighted that cephalosporin/β-lactamase inhibitors are potential selectors of MDR/XDR P. aeruginosa strains producing PDC variants or metallo-β-lactamases. Judicious use of these agents is encouraged.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/aac.02067-21
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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  • 10
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    Nasopharyngeal Expression of Angiotensin-Converting Enzyme 2 and Transmembrane Serine Protease 2 in Children within SARS-CoV-2-Infected Family Clusters
    American Society for Microbiology ; 2021
    In:  Microbiology Spectrum Vol. 9, No. 3 ( 2021-12-22)
    Details
    In: Microbiology Spectrum, American Society for Microbiology, Vol. 9, No. 3 ( 2021-12-22)
    Abstract: Lower levels of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in the nasal epithelium of children may be related to a lower incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, compared to adults. However, no direct evidence is available to support this hypothesis. In this study, we compared the transcript levels of ACE2 and TMPRSS2 in nasopharyngeal swab samples ( n  = 234) from children and adult family members within SARS-CoV-2-exposed families and assessed the association with SARS-CoV-2 infection status. Transcript levels for ACE2, but not TMPRSS2, were higher in adults than in children ( n  = 129 adults and 105 children; P  〈   0.05). The expression of the two genes was not significantly different between SARS-CoV-2 positive and SARS-CoV-2 negative patients within the same age groups. However, in families with one or more SARS-CoV-2 positive adult family members, expression of both genes was significantly higher in SARS-CoV-2 positive children than in SARS-CoV-2 negative children ( P  〈   0.05). By multivariate analysis, ACE2 expression adjusted for age and sex was significantly associated with SARS-CoV-2 infection in the overall population (odds ratio [OR], 1.112 [95% confidence interval [CI] , 1.012 to 1.229]; P  〈   0.05). The degree of this association was higher (OR, 1.172 [95% CI, 1.034 to 1.347]; P  〈   0.05) in the subgroup of families with only SARS-CoV-2 positive adult family members. Our results suggest that children with lower levels of nasal ACE2 and TMPRSS2 are more likely to remain SARS-CoV-2 negative despite being exposed to a SARS-CoV-2 positive adult family member. IMPORTANCE ACE2 and TMPRSS2 are well established in the literature as SARS-CoV-2 entry factors. Recent data suggest that lower levels of nasal ACE2 in children may be associated with their lower incidence of coronavirus disease 2019 (COVID-19). In this study, using data from nasopharyngeal swab specimens from adult and pediatric members of families in which one or more members of the family had laboratory-confirmed SARS-CoV-2 infection, we show that children with lower levels of ACE2 and TMPRSS2 are more likely to remain SARS-CoV-2 negative despite being exposed to a SARS-CoV-2 positive adult family member. These results provide new insights into the roles of nasopharyngeal ACE2 and TMPRSS2 in acquiring SARS-CoV-2 infection, and they show that the differential expression of these genes in adults versus children may contribute to differential rates of SARS-CoV-2 infection in these populations.
    Type of Medium: Online Resource
    ISSN: 2165-0497
    URL: Article
    DOI: 10.1128/Spectrum.00783-21
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2021
    detail.hit.zdb_id: 2807133-5
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