Molecular investigations on a chimeric strain of Staphylococcus aureus sequence type 80

Abstract

A PVL-positive, methicillin-susceptible Staphylococcus aureus was cultured from pus from cervical lymphadenitis of a patient of East-African origin. Microarray hybridisation assigned the isolate to clonal complex (CC) 80 but revealed unusual features, including the presence of the ORF-CM14 enterotoxin homologue and of an ACME-III element as well as the absence of etD and edinB. The isolate was subjected to both, Illumina and Nanopore sequencing allowing characterisation of deviating regions within the strain´s genome. Atypical features of this strain were attributable to the presence of two genomic regions that originated from other S. aureus lineages and that comprised, respectively, 3% and 1.4% of the genome. One deviating region extended from walJ to sirB. It comprised ORF-CM14 and the ACME-III element. A homologous but larger fragment was also found in an atypical S. aureus CC1/ST567 strain whose lineage might have served as donor of this genomic region. This region itself is a chimera comprising fragments from CC1 as well as fragments of unknown origin. The other deviating region comprised the region from htsB to ecfA2, i.e., another 3% of the genome. It was very similar to CC1 sequences. Either this suggests an incorporation of CC1 DNA into the study strain, or alternatively a recombination event affecting "canonical" CC80. Thus, the study strain bears witness of several recombination events affecting supposedly core genomic genes. Although the exact mechanism is not yet clear, such chimerism seems to be an additional pathway in the evolution of S. aureus. This could facilitate also a transmission of virulence and resistance factors and therefore offer an additional evolutionary advantage.

Characterisation and Molecular Analysis of an Unusual Chimeric Methicillin Resistant Staphylococcus Aureus Strain and its Bacteriophages

“…In summary, three practically relevant conclusions can be drawn from this study. First, evolution by large scale chromosomal replacements appear to be more common in the evolutionary history of S. aureus than previously appreciated as there is an increasing number of strains that can be described as chimeras combining genes and alleles from unrelated lineages ( Robinson and Enright, 2004 ; Monecke et al, 2011 ; Budd et al, 2015 ; Nimmo et al, 2015 ; Fetsch et al, 2017 ; Monecke et al, 2018 ; Gawlik et al, 2020 ) although the mechanisms are not yet understood. Second, xis genes of SaPIs might enable the mobilisation of bacteriophages that do not carry XIS themselves.…”

“…Another strain, ST2249, harbours CC239 DNA comprising fragments of both, CC8 and CC30 that is integrated into a CC45 genome ( Nimmo et al, 2015 ). Further examples for chimeric strains are ST34/ST42 (where CC10 fragments are integrated into CC30 genomes ( Robinson and Enright, 2004 )), CC398 strains that harbour fragments of CC9 origin ( Fetsch et al, 2017 ; Monecke et al, 2018 ), a CC80 strain incorporating two separate fragments of DNA from CC1 and an unknown donor strain ( Gawlik et al, 2020 ), ST71 in which a region of unknown origin is integrated into a CC97 genome ( Budd et al, 2015 ) as well as two MRSA strains (ST1048 and ST1774) from Hong Kong ( Monecke et al, 2011 ). While there are several examples in which large scale genomic replacements or chimerism explain unusual features of strains that cannot be attributed to more conventional means of lateral gene transfer, the mechanism of transfer and integration of literally 100,000s nucleotides of core genome has yet to be elucidated.…”

Sequence Analysis of Novel Staphylococcus aureus Lineages from Wild and Captive Macaques

“…A total of 157 genomes were analysed. For the sake of simplicity, genomes of strains that were known to be chimeras or hybrids, consisting of fragments originating from unrelated parental lineages, were excluded (ST34, ST71, variant ST80, ST239, ST567, ST2249, and ST6610; [ 63 , 64 , 65 , 66 , 67 ]). Genes and strains are listed in Supplemental File S3 .…”

Recombination in Bacterial Genomes: Evolutionary Trends

“…The consequences of such instances are illustrated by the examples of Vibrio parahaemolyticus outbreaks that occurred after large genome rearrangements around O- and K-antigenic regions [ 113 ], hypervirulent strains of K. pneumonia that underwent 100 kb-long exchanges [ 114 ], or strains of Legionella pneumophila and Streptococcus agalactiae , subjected to similar events throughout their evolutionary history [ 115 , 116 ]. In Staphylococcus aureus, such recombination-induced rearrangements cause not only hybrid strain formation [ 117 ], but also the extension of infectious potential by gaining the ability to colonize ruminants [ 118 ].…”