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Bartonella henselae is the causative agent of cat scratch disease and other clinical entities such as endocarditis and bacillary angiomatosis. The life cycle of this pathogen, with alternating host conditions, drives evolutionary and host-specific adaptations. Human, feline, and laboratory adapted B. henselae isolates often display genomic and phenotypic differences that are related to the expression of outer membrane proteins, for example the Bartonella adhesin A (BadA). This modularly-structured trimeric autotransporter adhesin is a major virulence factor of B. henselae and is crucial for the initial binding to the host via the extracellular matrix proteins fibronectin and collagen. By using next-generation long-read sequencing we demonstrate a conserved genome among eight B. henselae isolates and identify a variable genomic badA island with a diversified and highly repetitive badA gene flanked by badA pseudogenes. Two of the eight tested B. henselae strains lack BadA expression because of frameshift mutations. We suggest that active recombination mechanisms, possibly via phase variation (i.e., slipped-strand mispairing and site-specific recombination) within the repetitive badA island facilitate reshuffling of homologous domain arrays. The resulting variations among the different BadA proteins might contribute to host immune evasion and enhance long-term and efficient colonisation in the differing host environments. Considering the role of BadA as a key virulence factor, it remains important to check consistently and regularly for BadA surface expression during experimental infection procedures.
The current problem of increasing antibiotic resistance and the resurgence of numerous infections indicate the need for novel vaccination strategies more than ever. In vaccine development, the search for and the selection of adequate vaccine antigens is the first important step. In recent years, bacterial outer membrane proteins have become of major interest, as they are the main proteins interacting with the extracellular environment. Trimeric autotransporter adhesins (TAAs) are important virulence factors in many Gram-negative bacteria, are localised on the bacterial surface, and mediate the first adherence to host cells in the course of infection. One example is the Neisseria adhesin A (NadA), which is currently used as a subunit in a licensed vaccine against Neisseria meningitidis. Other TAAs that seem promising vaccine candidates are the Acinetobacter trimeric autotransporter (Ata), the Haemophilus influenzae adhesin (Hia), and TAAs of the genus Bartonella. Here, we review the suitability of various TAAs as vaccine candidates.
Objectives: Multidrug-resistant organisms (MDRO) are considered an emerging threat worldwide. Data covering the clinical impact of MDRO colonization in patients with solid malignancies, however, is widely missing. We sought to determine the impact of MDRO colonization in patients who have been diagnosed with Non-small cell lung cancer (NSCLC) who are at known high-risk for invasive infections.
Materials and methods: Patients who were screened for MDRO colonization within a 90-day period after NSCLC diagnosis of all stages were included in this single-center retrospective study.
Results: Two hundred and ninety-five patients were included of whom 24 patients (8.1%) were screened positive for MDRO colonization (MDROpos) at first diagnosis. Enterobacterales were by far the most frequent MDRO detected with a proportion of 79.2% (19/24). MDRO colonization was present across all disease stages and more present in patients with concomitant diabetes mellitus. Median overall survival was significantly inferior in the MDROpos study group with a median OS of 7.8 months (95% CI, 0.0–19.9 months) compared to a median OS of 23.9 months (95% CI, 17.6–30.1 months) in the MDROneg group in univariate (p = 0.036) and multivariate analysis (P = 0.02). Exploratory analyses suggest a higher rate of non-cancer-related-mortality in MDROpos patients compared to MDROneg patients (p = 0.002) with an increased rate of fatal infections in MDROpos patients (p = 0.0002).
Conclusions: MDRO colonization is an independent risk factor for inferior OS in patients diagnosed with NSCLC due to a higher rate of fatal infections. Empirical antibiotic treatment approaches should cover formerly detected MDR commensals in cases of (suspected) invasive infections.
OXA-48-like carbapenemases are among the most frequent carbapenemases in Gram-negative Enterobacterales worldwide with the highest prevalence in the Middle East, North Africa and Europe. Here, we investigated the so far uncharacterized carbapenemase OXA-484 from a clinical E. coli isolate belonging to the high-risk clone ST410 regarding antibiotic resistance pattern, horizontal gene transfer (HGT) and genetic support. OXA-484 differs by the amino acid substitution 214G compared to the most closely related variants OXA-181 (214R) and OXA-232 (214S). The blaOXA–484 was carried on a self-transmissible 51.5 kb IncX3 plasmid (pOXA-484) showing high sequence similarity with plasmids harboring blaOXA–181. Intraspecies and intergenus HGT of pOXA-484 to different recipients occurred at low frequencies of 1.4 × 10–7 to 2.1 × 10–6. OXA-484 increased MICs of temocillin and carbapenems similar to OXA-232 and OXA-244, but lower compared with OXA-48 and OXA-181. Hence, OXA-484 combines properties of OXA-181-like plasmid support and transferability as well as β-lactamase activity of OXA-232.
Molecular surveillance of carbapenem-resistant gram-negative bacteria in liver transplant candidates
(2021)
Background: Carbapenem-resistant Gram-negative bacteria (CRGN) cause life-threatening infections due to limited antimicrobial treatment options. The occurrence of CRGN is often linked to hospitalization and antimicrobial treatment but remains incompletely understood. CRGN are common in patients with severe illness (e.g., liver transplantation patients). Using whole-genome sequencing (WGS), we aimed to elucidate the evolution of CRGN in this vulnerable cohort and to reconstruct potential transmission routes.
Methods: From 351 patients evaluated for liver transplantation, 18 CRGN isolates (from 17 patients) were analyzed. Using WGS and bioinformatic analysis, genotypes and phylogenetic relationships were explored. Potential epidemiological links were assessed by analysis of patient charts.
Results: Carbapenem-resistant (CR) Klebsiella pneumoniae (n=9) and CR Pseudomonas aeruginosa (n=7) were the predominating pathogens. In silico analysis revealed that 14/18 CRGN did not harbor carbapenemase-coding genes, whereas in 4/18 CRGN, carbapenemases (VIM-1, VIM-2, OXA-232, and OXA-72) were detected. Among all isolates, there was no evidence of plasmid transfer-mediated carbapenem resistance. A close phylogenetic relatedness was found for three K. pneumoniae isolates. Although no epidemiological context was comprehensible for the CRGN isolates, evidence was found that the isolates resulted of a transmission of a carbapenem-susceptible ancestor before individual radiation into CRGN.
Conclusion: The integrative epidemiological study reveals a high diversity of CRGN in liver cirrhosis patients. Mutation of carbapenem-susceptible ancestors appears to be the dominant way of CR acquisition rather than in-hospital transmission of CRGN or carbapenemase-encoding genetic elements. This study underlines the need to avoid transmission of carbapenem-susceptible ancestors in vulnerable patient cohorts.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers potential cure to acute myeloid leukemia (AML) patients. However, infections with commensal bacteria are an important cause for non-relapse mortality (NRM). We have previously described the impact of multidrug-resistant organism (MDRO) colonization on the survival of allo-HSCT patients. In the aforementioned publication, according to consensus, we there did not consider the opportunistic gram-negative bacterium Stenotrophomonas maltophilia (S. maltophilia) to be an MDRO. Since rate of S. maltophilia colonization is increasing, and it is not known whether this poses a risk for allo-HSCT patients, we here analyzed here its effect on the previously described and now extended patient cohort. We report on 291 AML patients undergoing allo-HSCT. Twenty of 291 patients (6.9%) were colonized with S. maltophilia. Colonized patients did not differ from non-colonized patients with respect to their age, remission status before allo-HSCT, donor type and HSCT-comorbidity index. S. maltophilia colonized patients had a worse overall survival (OS) from 6 months up to 60 months (85% vs. 88.1% and 24.7% vs. 59.7%; p = 0.007) due to a higher NRM after allo-HSCT (6 months: 15% vs. 4.8% and 60 months: 40.1% vs. 16.2% p = 0.003). The main cause of mortality in colonized patients was infection (46.2% of all deaths) and in non-colonized patients relapse (58.8% of all deaths). 5/20 colonized patients developed an invasive infection with S. maltophilia. The worse OS after allo-HSCT due to higher infection related mortality might implicate the screening of allo-HSCT patients for S. maltophilia and a closer observation of colonized patients as outpatients.
Multidrug-resistant Gram-negative bacteria (MDR GNB) were found to colonise 60.8% (95% confidence interval: 52.3–68.9) of 143 refugee patients mainly from Syria (47), Afghanistan (29), and Somalia (14) admitted to the University Hospital Frankfurt, Germany, between June and December 2015. This percentage exceeds the prevalence of MDR GNB in resident patients four–fold. Healthcare personnel should be aware of this and the need to implement or adapt adequate infection control measures.
Infectious diseases remain a remarkable health threat for humans and animals. In the past, the epidemiology, etiology and pathology of infectious agents affecting humans and animals have mostly been investigated in separate studies. However, it is evident, that combined approaches are needed to understand geographical distribution, transmission and infection biology of “zoonotic agents”. The genus Bartonella represents a congenial example of the synergistic benefits that can arise from such combined approaches: Bartonella spp. infect a broad variety of animals, are linked with a constantly increasing number of human diseases and are transmitted via arthropod vectors. As a result, the genus Bartonella is predestined to play a pivotal role in establishing a One Health concept combining veterinary and human medicine.
The deer ked (Lipoptena cervi) is distributed in Europe, North America, and Siberia and mainly infests cervids as roe deer, fallow deer, and moose. From a one health perspective, deer keds occasionally bite other animals or humans and are a potential vector for Bartonella schoenbuchensis. This bacterium belongs to a lineage of ruminant-associated Bartonella spp. and is suspected to cause dermatitis and febrile diseases in humans. In this study, we analyzed the microbiome from 130 deer keds collected from roe deer, fallow deer and humans in the federal states of Hesse, Baden-Wuerttemberg, and Brandenburg, Germany. Endosymbiontic Arsenophonus spp. and Bartonella spp. represented the biggest portion (~90%) of the microbiome. Most Bartonella spp. (n = 93) were confirmed to represent B. schoenbuchensis. In deer keds collected from humans, no Bartonella spp. were detected. Furthermore, Acinetobacter spp. were present in four samples, one of those was confirmed to represent A. baumannii. These data suggest that deer keds harbor only a very narrow spectrum of bacteria which are potentially pathogenic for animals of humans.