Novel nonsense mutation in the katA gene of a catalase-negative Staphylococcus aureus strain

Abstract We report the first description of a rare catalase-negative strain of Staphylococcus aureus in Chile. This new variant was isolated from blood and synovial tissue samples of a pediatric patient. Sequencing analysis revealed that this catalase-negative strain is related to ST10 strain, which has earlier been described in relation to S. aureus carriers. Interestingly, sequence analysis of the catalase gene katA revealed presence of a novel nonsense mutation that causes premature translational truncation of the C-terminus of the enzyme leading to a loss of 222 amino acids. Our study suggests that loss of catalase activity in this rare catalase-negative Chilean strain is due to this novel nonsense mutation in the katA gene, which truncates the enzyme to just 283 amino acids

Regulatory T Cells Are Locally Induced during Intravaginal Infection of Mice with Neisseria gonorrhoeae▿

Neisseria gonorrhoeae is a gram-negative diplococcus that in human beings produces gonorrhea. Much clinical evidence has led to the conclusion that gonococcus has important mechanisms to evade host immune functions; however, these mechanisms are only now beginning to be elucidated. In this study, we determined that the BALB/c mouse is a good animal model to study gonococcus infection and examined the immune response against the bacteria. We determined that after intravaginal inoculation of mice with Neisseria gonorrhoeae, the bacteria reached and invaded the upper female reproductive tissues and elicited a T-cell-specific immune response associated with a very weak humoral response, altogether resembling gonococcus infection and disease in women. Remarkably, in the draining lymph nodes of the genital tracts of infected mice, we found an increase of regulatory T lymphocytes, namely, transforming growth factor β1-positive CD4+ T cells and CD4+ CD25+ Foxp3+ T cells. Altogether, results indicate that N. gonorrhoeae induces regulatory T cells, which might be related to the local survival of the pathogen and the establishment of a chronic asymptomatic infection

Analysis of <i>Mycobacterium tuberculosis</i> Genotypic Lineage Distribution in Chile and Neighboring Countries

<div><p>Tuberculosis (TB), caused by the pathogen <i>Mycobacterium tuberculosis</i> (MTB), remains a disease of high importance to global public health. Studies into the population structure of MTB have become vital to monitoring possible outbreaks and also to develop strategies regarding disease control. Although Chile has a low incidence of MTB, the current rates of migration have the potential to change this scenario. We collected and analyzed a total of 458 <i>M</i>. <i>tuberculosis</i> isolates (1 isolate per patient) originating from all 15 regions of Chile. The isolates were genotyped using the spoligotyping method and the data obtained were analyzed and compared with the SITVIT2 database. A total of 169 different patterns were identified, of which, 119 patterns (408 strains) corresponded to Spoligotype International Types (SITs) and 50 patterns corresponded to orphan strains. The most abundantly represented SITs/lineages were: SIT53/T1 (11.57%), SIT33/LAM3 (9.6%), SIT42/LAM9 (9.39%), SIT50/H3 (5.9%), SIT37/T3 (5%); analysis of the spoligotyping minimum spanning tree as well as spoligoforest were suggestive of a recent expansion of SIT42, SIT50 and SIT37; all of which potentially evolved from SIT53. The most abundantly represented lineages were LAM (40.6%), T (34.1%) and Haarlem (13.5%). LAM was more prevalent in the Santiago (43.6%) and Concepción (44.1%) isolates, rather than the Iquique (29.4%) strains. The proportion of X lineage was appreciably higher in Iquique and Concepción (11.7% in both) as compared to Santiago (1.6%). Global analysis of MTB lineage distribution in Chile versus neighboring countries showed that evolutionary recent lineages (LAM, T and Haarlem) accounted together for 88.2% of isolates in Chile, a pattern which mirrored MTB lineage distribution in neighboring countries (n = 7378 isolates recorded in SITVIT2 database for Peru, Brazil, Paraguay, and Argentina; and published studies), highlighting epidemiological advantage of Euro-American lineages in this region. Finally, we also observed exclusive emergence of patterns SIT4014/X1 and SIT4015 (unknown lineage signature) that have hitherto been found exclusively in Chile, indicating that conditions specific to Chile, along with the unique genetic makeup of the Chilean population, might have allowed for a possible co-evolution leading to the success of these emerging genotypes.</p></div

Description of clusters containing >1% (n = 5 or more isolates) in this study, and their worldwide distribution in the SITVIT2 database.

<p>Description of clusters containing >1% (n = 5 or more isolates) in this study, and their worldwide distribution in the SITVIT2 database.</p

Spoligoforest tree based on all spoligotypes (n = 458 isolates).

<p>Spoligoforest was drawn using the Fruchterman-Reingold algorithm from the SpolTools software (<a href="http://www.emi.unsw.edu.au/spolTools" target="_blank">http://www.emi.unsw.edu.au/spolTools</a>)[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0160434#pone.0160434.ref029" target="_blank">29</a>], and reshaped and colored using the GraphViz software (<a href="http://www.graphviz.org/" target="_blank">http://www.graphviz.org</a>)[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0160434#pone.0160434.ref030" target="_blank">30</a>]. Each spoligotype pattern from the study is represented by a node with area size being proportional to the total number of isolates with that specific pattern. Changes (loss of spacers) are represented by directed edges between nodes, with the arrowheads pointing to descendant spoligotypes. The heuristic used selects a single inbound edge with a maximum weight using a Zipf model. Solid black lines link patterns that are very similar, i.e., loss of one spacer only (maximum weigh being 1.0), while dashed lines represent links of weight comprised between 0.5 and 1, and dotted lines a weight less than 0.5.</p

Description of 119 shared-types (SITs; n = 408 isolates) and corresponding spoligotyping defined lineages/sublineages starting from a total of 458 <i>M</i>. <i>tuberculosis</i> strains isolated in various cities in Chile.

<p>Description of 119 shared-types (SITs; n = 408 isolates) and corresponding spoligotyping defined lineages/sublineages starting from a total of 458 <i>M</i>. <i>tuberculosis</i> strains isolated in various cities in Chile.</p

A comparison of the proportion of predominant SITs found in Chile (n = 458 isolates in total, as well as distribution patterns for major cities, i.e., Santiago, Iquique, and Concepción), as compared to neighboring countries (Peru, Brazil, Paraguay, Argentina), recorded in the SITVIT2 database.

<p>A comparison of the proportion of predominant SITs found in Chile (n = 458 isolates in total, as well as distribution patterns for major cities, i.e., Santiago, Iquique, and Concepción), as compared to neighboring countries (Peru, Brazil, Paraguay, Argentina), recorded in the SITVIT2 database.</p

Phylogeographical distribution of <i>M</i>. <i>tuberculosis</i> lineages identified in our study and MST illustrating evolutionary relationships.

<p>(A) Phylogeographical distribution of major <i>M</i>. <i>tuberculosis</i> lineages in the 3 most important cities in our study (Santiago, Iquique, Concepción) as well as following neighboring countries: Peru, Brazil, and Paraguay (referring to the SITVIT2 database). (B) A minimum spanning tree (MST) illustrating evolutionary relationships between spoligotypes in various cities of Chile (n = 458 isolates). The phylogenetic tree connects each genotype based on degree of changes required to go from one allele to another. The structure of the tree is represented by branches (continuous vs. dashed and dotted lines) and circles representing each individual pattern. Note that the length of the branches represents the distance between patterns while the complexity of the lines (continuous, gray dashed and gray dotted) denotes the number of allele/spacer changes between two patterns: solid lines, 1 or 2 or 3 changes (thicker ones indicate a single change, while the thinner ones indicate 2 or 3 changes); gray dashed lines represent 4 changes; and gray dotted lines represent 5 or more changes. The size of the circle is proportional to the total number of isolates in our study, illustrating unique isolates (smaller nodes) versus clustered isolates (bigger nodes). The color of the circles indicates the phylogenetic lineage to which the specific pattern belongs. The labels of nodes indicate predominant SITs in study (containing at least 5 or more isolates).</p