Global Expansion of Linezolid-Resistant Coagulase-Negative Staphylococci

Coagulase-negative staphylococci (CoNS) for a long time were considered avirulent constituents of the human and warm-blooded animal microbiota. However, at present, S. epidermidis, S. haemolyticus, and S. hominis are recognized as opportunistic pathogens. Although linezolid is not registered for the treatment of CoNS infections, it is widely used off-label, promoting emergence of resistance. Bioinformatic analysis based on maximum-likelihood phylogeny and Bayesian clustering of the CoNS genomes obtained in the current study and downloaded from public databases revealed the existence of international linezolid-resistant lineages, each of which probably had a common predecessor. Linezolid-resistant S. epidermidis sequence-type (ST) 2 from Russia, France, and Germany formed a compact group of closely related genomes with a median pairwise single nucleotide polymorphism (SNP) difference of fewer than 53 SNPs, and a common ancestor of this lineage appeared in 1998 (1986–2006) before introduction of linezolid in practice. Another compact group of linezolid-resistant S. epidermidis was represented by ST22 isolates from France and Russia with a median pairwise SNP difference of 40; a common ancestor of this lineage appeared in 2011 (2008–2013). Linezolid-resistant S. hominis ST2 from Russia, Germany, and Brazil also formed a group with a high-level genome identity with median 25.5 core-SNP differences; the appearance of the common progenitor dates to 2003 (1996–2012). Linezolid-resistant S. hominis isolates from Russia demonstrated associated resistance to teicoplanin. Analysis of a midpoint-rooted phylogenetic tree of the group confirmed the genetic proximity of Russian and German isolates; Brazilian isolates were phylogenetically distant. repUS5-like plasmids harboring cfr were detected in S. hominis and S. haemolyticus.

Genomic analysis and phylogenetic position of the complex IncC plasmid found in the Spanish monophasic clone of Salmonella enterica serovar Typhimurium

AbstractpUO-STmRV1 is an IncC plasmid discovered in the Spanish clone of the emergent monophasic variant of Salmonella enterica serovar Typhimurium, which has probably contributed to its epidemiological success. The sequence of the entire plasmid determined herein revealed a largely degenerated backbone with accessory DNA incorporated at four different locations. The acquired DNA constitutes more than two-thirds of the pUO-STmRV1 genome and originates from plasmids of different incompatibility groups, including IncF (such as R100 and pSLT, the virulence plasmid specific of S. Typhimurium), IncN and IncI, from the integrative element GIsul2, or from yet unknown sources. In addition to pSLT virulence genes, the plasmid carries genes conferring resistance to widely-used antibiotics and heavy metals, together with a wealth of genetic elements involved in DNA mobility. The latter comprise class 1 integrons, transposons, pseudo-transposons, and insertion sequences, strikingly with 14 copies of IS26, which could have played a crucial role in the assembly of the complex plasmid. Typing of pUO-STmRV1 revealed backbone features characteristically associated with type 1 and type 2 IncC plasmids and could therefore be regarded as a hybrid plasmid. However, a rooted phylogenetic tree based on core genes indicates that it rather belongs to an ancient lineage which diverged at an early stage from the branch leading to most extant IncC plasmids detected so far. pUO-STmRV1 may have evolved at a time when uncontrolled use of antibiotics and biocides favored the accumulation of multiple resistance genes within an IncC backbone. The resulting plasmid thus allowed the Spanish clone to withstand a wide variety of adverse conditions, while simultaneously promoting its own propagation through vertical transmission.

On Sackin's original proposal: The variance of the leaves' depths as a phylogenetic balance index

Background. The Sackin index S of a rooted phylogenetic tree, defined as the sum of its leaves' depths, is one of the most popular balance indices in phylogenetics, and Sackin's 1972 paper is usually cited as the source for this index. However, what Sackin actually proposed in his paper as a measure of the imbalance of a rooted tree was not the sum of its leaves' depths, but their ``variation''. This proposal was later implemented as the variance of the leaves' depths by Kirkpatrick and Slatkin in 1993, where they also posed the problem of finding a closed formula for its expected value under the Yule model. Nowadays, Sackin's original proposal seems to have passed into oblivion in the phylogenetics literature, replaced by the index bearing his name, which, in fact, was introduced a decade later by Sokal. Results. In this paper we study the properties of the variance of the leaves' depths, V, as a balance index. Firstly, we prove that the rooted trees with $n$ leaves and maximum V value are exactly the combs with n leaves. But although V achieves its minimum value on every space of bifurcating rooted phylogenetic trees with at most 183 leaves at the so-called ``maximally balanced trees'' with n leaves, this property fails for almost every n larger than 184 We provide then an algorithm that finds the bifurcating rooted trees with n leaves and minimum V value in quasilinear time. Secondly, we obtain closed formulas for the expected V value of a bifurcating rooted tree with any number n of leaves under the Yule and the uniform models and, as a by-product of the computations leading to these formulas, we also obtain closed formulas for the variance under the uniform model of the Sackin index and the total cophenetic index of a bifurcating rooted tree, as well as of their covariance, thus filling this gap in the literature.

On Sackin's original proposal: The variance of the leaves' depths as a phylogenetic balance index

Background. The Sackin index S of a rooted phylogenetic tree, defined as the sum of its leaves' depths, is one of the most popular balance indices in phylogenetics, and Sackin's 1972 paper is usually cited as the source for this index. However, what Sackin actually proposed in his paper as a measure of the imbalance of a rooted tree was not the sum of its leaves' depths, but their ``variation''. This proposal was later implemented as the variance of the leaves' depths by Kirkpatrick and Slatkin in 1993, where they also posed the problem of finding a closed formula for its expected value under the Yule model. Nowadays, Sackin's original proposal seems to have passed into oblivion in the phylogenetics literature, replaced by the index bearing his name, which, in fact, was introduced a decade later by Sokal. Results. In this paper we study the properties of the variance of the leaves' depths, V, as a balance index. Firstly, we prove that the rooted trees with $n$ leaves and maximum V value are exactly the combs with n leaves. But although V achieves its minimum value on every space of bifurcating rooted phylogenetic trees with at most 183 leaves at the so-called ``maximally balanced trees'' with n leaves, this property fails for almost every n larger than 184 We provide then an algorithm that finds the bifurcating rooted trees with n leaves and minimum V value in quasilinear time. Secondly, we obtain closed formulas for the expected V value of a bifurcating rooted tree with any number n of leaves under the Yule and the uniform models and, as a by-product of the computations leading to these formulas, we also obtain closed formulas for the variance under the uniform model of the Sackin index and the total cophenetic index of a bifurcating rooted tree, as well as of their covariance, thus filling this gap in the literature.

On Sackin's original proposal: The variance of the leaves' depths as a phylogenetic balance index

Background: The Sackin index S of a rooted phylogenetic tree, defined as the sum of its leaves' depths, is one of the most popular balance indices in phylogenetics, and Sackin's 1972 paper is usually cited as the source for this index. However, what Sackin actually proposed in his paper as a measure of the imbalance of a rooted tree was not the sum of its leaves' depths, but their "variation". This proposal was later implemented as the variance of the leaves' depths by Kirkpatrick and Slatkin, where moreover they posed the problem of finding a closed formula for its expected value under the Yule model. Nowadays, Sackin's original proposal seems to have passed into oblivion in the phylogenetics literature, replaced by the index bearing his name, which, in fact, was introduced a decade later by Sokal.Results: In this paper we study the properties of the variance of the leaves' depths, V, as a balance index. Firstly, we prove that the rooted trees with n leaves and maximum V value are exactly the combs with n leaves. But although V achieves its minimum value on every space BT_n of bifurcating rooted phylogenetic trees with n< 184 leaves at the so-called "maximally balanced trees" with n leaves, this property fails for almost every n>= 184. We provide then an algorithm that finds in O(n) time the trees in BT_n with minimum V value. Secondly, we obtain closed formulas for the expected V value of a bifurcating rooted tree with any number n of leaves under the Yule and the uniform models and, as a by-product of the computations leading to these formulas, we also obtain closed formulas for the variance of the Sackin index and the total cophenetic indexof a bifurcating rooted tree, as well as of their covariance, under the uniform model, thus filling this gap in the literature.Conclusions: The phylogenetics crowd has been wise in preferring as a balance index the sum S(T) of the leaves’ depths of a phylogenetic tree T over their variance V (T), because the latter does not seem to capture correctly the notion of balance of large bifurcating rooted trees. But for bifurcating trees up to 183 leaves, V is a valid and useful balance index.

The combinatorics of discrete time-trees: theory and open problems

ABSTRACTA time-tree is a rooted phylogenetic tree such that all internal nodes are equipped with absolute divergence dates and all leaf nodes are equipped with sampling dates. Such time-trees have become a central object of study in phylogenetics but little is known about the parameter space of such objects. Here we introduce and study a hierarchy of discrete approximations of the space of time-trees from the graph-theoretic and algorithmic point of view. One of the basic and widely used phylogenetic graphs, the NNI graph, is the roughest approximation and bottom level of our hierarchy. More refined approximations discretize the relative timing of evolutionary divergence and sampling dates. We study basic graph-theoretic questions for these graphs, including the size of neighborhoods, diameter upper and lower bounds, and the problem of finding shortest paths. We settle many of these questions by extending the concept of graph grammars introduced by Sleator, Tarjan, and Thurston to our graphs. Although time values greatly increase the number of possible trees, we show that 1-neighborhood sizes remain linear, allowing for efficient local exploration and construction of these graphs. We also obtain upper bounds on the r-neighborhood sizes of these graphs, including a smaller bound than was previously known for NNI.Our results open up a number of possible directions for theoretical investigation of graph-theoretic and algorithmic properties of the time-tree graphs. We discuss the directions that are most valuable for phylogenetic applications and give a list of prominent open problems for those applications. In particular, we conjecture that the split theorem applies to shortest paths in time-tree graphs, a property not shared in the general NNI case.