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Antimicrobial resistance in Neisseria gonorrhoeae is an important global health concern. The genetically related commensal Neisseria act as a reservoir of resistance genes, and horizontal gene transfer (HGT) has been shown to play an important role in the genesis of resistance to cephalosporins and macrolides in N. gonorrhoeae. In this study, we evaluated if there was evidence of HGT in the genes gyrA/gyrB and parC/parE responsible for fluoroquinolone resistance. Even though the role of gyrB and parE in quinolone resistance is unclear, the subunits gyrB and parE were included as zoliflodacin, a promising new drug to treat N. gonorrhoeae targets the gyrB subunit. We analyzed a collection of 20,047 isolates; 18,800 N. gonorrhoeae, 1,238 commensal Neisseria spp., and nine Neisseria meningitidis. Comparative genomic analyses identified HGT events in genes, gyrA, gyrB, parC, and parE. Recombination events were predicted in N. gonorrhoeae and Neisseria commensals. Neisseria lactamica, Neisseria macacae, and Neisseria mucosa were identified as likely progenitors of the HGT events in gyrA, gyrB, and parE, respectively.

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Original Research
07 February 2022
Long-Read Sequencing Reveals Genetic Adaptation of Bartonella Adhesin A Among Different Bartonella henselae Isolates
Arno Thibau
7 more and 
Volkhard A. J. Kempf

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.

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Whether and how adaptive evolution adjusts the breadth of adaptation in coordination with the genome are essential issues for connecting evolution with ecology. To address these questions, experimental evolution in five Escherichia coli strains carrying either the wild-type genome or a reduced genome was performed in a defined minimal medium (C0). The ancestral and evolved populations were subsequently subjected to fitness and chemical niche analyses across an environmental gradient with 29 combinations of eight chemical components of the minimal medium. The results showed that adaptation was achieved not only specific to the evolutionary condition (C0), but also generally, to the environmental gradient; that is, the breadth of adaptation to the eight chemical niches was expanded. The magnitudes of the adaptive improvement and the breadth increase were both correlated with genome reduction and were highly significant in two out of eight niches (i.e., glucose and sulfate). The direct adaptation-induced correlated adaptation to the environmental gradient was determined by only a few genome mutations. An additive increase in fitness associated with the stepwise fixation of mutations was consistently observed in the reduced genomes. In summary, this preliminary survey demonstrated that evolution finely tuned the breadth of adaptation correlated with genome reduction.

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8 citations
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