UNDER CONSTRUCTION.
ANTIBIOTIC RESISTANCE GENES
Mutations in specific genes are known to contribute to antibiotic resistance in bacteria. A rapidly growing global problem is posed by the increase in the number of infections caused by antibiotic-resistant bacteria. Bacteria that can cause disease in humans or in domesticated animals become resistant when mutations occur in the DNA of a cell and are amplified in the population by selection of resistant cells. Alternatively, a bacterium may acquire resistance genes from other, often harmless, bacteria by means of horizontal transfer, often mediated by plasmids, but sometimes simply by acquiring the DNA of dead cells from the environment.
The evidence for true, genetically mediated antibiotic resistance in scrub typhus is equivocal. Nevertheless, the genome of O. tsutsugamushi has the potential to produce resistance against a variety of anti-microbial compounds. Here, we will review the evidence for potential genetically mediated antibiotic resistance in O. tsutsugamushi.
GENOMES AND ANTIBIOTIC RESISTANCE
One approach to searching for the basis of antibiotic resistance in Orientia would be to examine the genome sequences of various scrub typhus isolates that are now becoming increasingly available for study. Searching for sequences that have homology with genes known to facilitate antibiotic resistance in other organisms is an approach that can be used.
We have begun to examine the genome sequences of isolates of Orientia for the presence or absence of genes that may contribute to potential antibiotic resistance. With more than 30 genome sequences now available, a search can be performed for nucleotide sequences that have homology with genes in other organisms that are known to facilitate antibiotic resistance. Several such genes appear to be present in the genomes of O. tsutsugamushi.
SPECIFIC GENES:
Genomes of scrub typhus isolates are being examined for the presence of putative resistance genes. Several such genes have been identified in the genomes of most (probably all) isolates of O. tsutsugamushi. (As of October 2017, genomes from 14 isolates have been studied; this will be expanded to all genome sequences in the future). In addition, the genome sequence of O. chuto has also been examined. Where we have identified these genes, we have listed the genome location within the Boryong isolate as a reference (since this isolate represents the initial isolate of O. tsutsugamushi for which a genome sequence was determined).
The genes or gene categories that may have the potential to affect levels of resistance to antibiotics include the following (links are provided to sub-pages describing the specific genes/mechanisms in genomes of Orientia, and the gene location in Boryong) :
gyrA : DNA gyrase
Bcr/CflA drug resistance efflux transporter
ABC-type multidrug transport system (includes genes for ATPase and permease components, genes for ATP-binding protein, and genes for substrate binding).
RND family efflux transporters
ampG1 – permease of the major facilitator superfamily
Microcin C resistance proteins
Additional Genes such as those involved in resistance to Macrolide, lincosamide, and streptogramin (MLS) antibiotics that affect RNA or DNA synthesis and that have known resistance mutations in other bacteria
ABSENCE OF GENES INVOLVED IN RESISTANCE
Also important for consideration is the absence of specific genes that could be inhibited by antibiotics. Specific examples include mechanisms of resistance to sulfamethoxazole or trimethoprim.
In examining the genomes of scrub typhus isolates, at least thirteen genes that were present in Rickettsia bellii do not have any significant homologous gene in any isolate of O. tsutsugamushi or in O. chuto. These genes are listed on a subpage for absent genes in scrub typhus.
SEE ADDITIONAL DETAILS ON PAGE FOR ANTIBIOTIC RESISTANCE.