A good career start can open doors: the plusses and minuses of an international graduate student program-a student's perspective.

There are many Ph.D. programs from various funding agencies that provide excellent starts to a scientific career. Multinational Ph.D. positions attract students because they provide students with much-required exposure to the international scientific community at an early stage of the career. For this reason, multinational Ph.D. positions can be considered as a better career opportunity over Ph.D. positions confined to a single country. In addition, these multidisciplinary research programs connect different organizations to deal with the problems of global interest. One of these multi-disciplinary research programs is the viral and bacterial adhesion network training-innovative training network (ViBrANT). ViBrANT is a multifaceted platform that develops the required skillsets in young researchers and thereby also contributes to building a multidisciplinary research community. Is this the only parameter to be considered or are there other factors that can also stimulate one's career development? In this perspective article, I will discuss the key reasons why I chose a multinational Ph.D. program along with the merits of being part of ViBrANT. I also discuss the challenges I faced while moving from India to the United Kingdom.

Recent advances in the understanding of trimeric autotransporter adhesins.

Adhesion is the initial step in the infection process of gram-negative bacteria. It is usually followed by the formation of biofilms that serve as a hub for further spread of the infection. Type V secretion systems engage in this process by binding to components of the extracellular matrix, which is the first step in the infection process. At the same time they provide protection from the immune system by either binding components of the innate immune system or by establishing a physical layer against aggressors. Trimeric autotransporter adhesins (TAAs) are of particular interest in this family of proteins as they possess a unique structural composition which arises from constraints during translocation. The sequence of individual domains can vary dramatically while the overall structure can be very similar to one another. This patchwork approach allows researchers to draw conclusions of the underlying function of a specific domain in a structure-based approach which underscores the importance of solving structures of yet uncharacterized TAAs and their individual domains to estimate the full extent of functions of the protein a priori. Here, we describe recent advances in understanding the translocation process of TAAs and give an overview of structural motifs that are unique to this class of proteins. The role of BpaC in the infection process of Burkholderia pseudomallei is highlighted as an exceptional example of a TAA being at the centre of infection initiation.

Increased number of teeth predict acquisition of mutans streptococci in infants.

This longitudinal study of 194 very-low birthweight (VLBW) and 184 normal birthweight (NBW) infants hypothesized that the causal pathway between birth group (VLBW or NBW) and mutans streptococci (MS) acquisition (presence) at 18-20 months is mediated by biological, behavioral, and caregiver MS levels. Biological (number of teeth at 8 and 18-20 months and enamel hypoplasia) and behavioral (brushing/cleaning, sweet snacks, breastfeeding, and dental access) factors were assessed using dental examinations and caregiver questionnaire responses at 8 and 18-20 months. Infant MS acquisition and caregiver MS levels were assessed from saliva and plaque samples collected at 8 and 18-20 months. Structural equation modeling evaluated the causal pathway with latent variables for biology and behavior. Mutans streptococci presence was similar between birth groups at 18-20 months (40% in VLBW infants and 49% in NBW infants), but was significantly higher for NBW infants at 8 months. Increased number of teeth at 8 and 18-20 months was associated with biological risk. Infants whose caregivers had a 1-point higher score on MS had a significantly (1.5) higher odds of MS presence. Caregiver behavior was not associated with MS presence. Early-intervention efforts should focus on delaying initial acquisition and improving caregiver awareness of taking care of erupting primary teeth.

Host-Pathogen Adhesion as the Basis of Innovative Diagnostics for Emerging Pathogens.

Infectious diseases are an existential health threat, potentiated by emerging and re-emerging viruses and increasing bacterial antibiotic resistance. Targeted treatment of infectious diseases requires precision diagnostics, especially in cases where broad-range therapeutics such as antibiotics fail. There is thus an increasing need for new approaches to develop sensitive and specific in vitro diagnostic (IVD) tests. Basic science and translational research are needed to identify key microbial molecules as diagnostic targets, to identify relevant host counterparts, and to use this knowledge in developing or improving IVD. In this regard, an overlooked feature is the capacity of pathogens to adhere specifically to host cells and tissues. The molecular entities relevant for pathogen-surface interaction are the so-called adhesins. Adhesins vary from protein compounds to (poly-)saccharides or lipid structures that interact with eukaryotic host cell matrix molecules and receptors. Such interactions co-define the specificity and sensitivity of a diagnostic test. Currently, adhesin-receptor binding is typically used in the pre-analytical phase of IVD tests, focusing on pathogen enrichment. Further exploration of adhesin-ligand interaction, supported by present high-throughput "omics" technologies, might stimulate a new generation of broadly applicable pathogen detection and characterization tools. This review describes recent results of novel structure-defining technologies allowing for detailed molecular analysis of adhesins, their receptors and complexes. Since the host ligands evolve slowly, the corresponding adhesin interaction is under selective pressure to maintain a constant receptor binding domain. IVD should exploit such conserved binding sites and, in particular, use the human ligand to enrich the pathogen. We provide an inventory of methods based on adhesion factors and pathogen attachment mechanisms, which can also be of relevance to currently emerging pathogens, including SARS-CoV-2, the causative agent of COVID-19.

A novel mutation alters the stability of PapA2 resulting in the complete abrogation of sulfolipids in clinical mycobacterial strains.

The analysis of whole genomes has revealed specific geographical distribution of Mycobacterium tuberculosis (Mtb) strains across the globe suggestive of unique niche dependent adaptive mechanisms. We provide an important correlation of a genome-based mutation to a molecular phenotype across two predominant clinical Mtb lineages of the Indian subcontinent. We have identified a distinct lineage specific mutation-G247C, translating into an alanine-proline conversion in the papA2 gene of Indo-oceanic lineage 1 (L1) Mtb strains, and restoration of cell wall sulfolipids by simple genetic complementation of papA2 from lineage 3 (L3) or from H37Rv (lineage 4-L4) attributed the loss of this glycolipid to this specific mutation in Indo-Oceanic L1 Mtb. The investigation of structure of Mtb PapA2 revealed a distinct nonribosomal peptide synthetase (NRPS) C domain conformation with an unconventional presence of a zinc binding motif. Surprisingly, the A83P mutation did not map to either the catalytic center in the N-terminal subdomain or any of the substrate-binding region of the protein. On the contrary, the inherent ability of mutant PapA2 to form insoluble aggregates and molecular simulations with the wild-type/mutant (Wt/mut) PapA2 purports an important role for the surface associated 83rd residue in protein conformation. This study demonstrates the importance of a critical structural residue in the papA2 protein of Mtb and helps establish a link between observed genomic alteration and its molecular consequence in the successful human pathogen Mtb. Significance We demonstrate the effect of a unique SNP in PapA2 gene of Indo-oceanic Mycobacterium tuberculosis (Mtb) strains leading to the loss of sulfolipid from these strains. By X-ray crystallographic analysis and molecular dynamics (MD) simulations, we show the importance of this residue in the global PapA2 structure. The presence of a Zn atom has not been reported before for this class of proteins. Here, we provide an important link between genomic alteration and its molecular consequence in Mtb highlighting one of the many adaptive mechanisms that have contributed to its success as a human pathogen. A high degree of identity with PapA1, 3, or 4 would help in interpreting the structure of these PapA proteins and other acyl transferases of other biological systems.

Mother's Perceived Social Support and Children's Dental Caries in Northern Appalachia.

Purpose: The purpose of this study was to examine whether perceived social support among mothers with high levels of dental caries was associated with their children experiencing high levels of dental caries. Methods: In West Virginia and Pennsylvania from 2002 to 2009, mothers were interviewed and clinical exams were conducted on their one- to six-year-old children. Two hundred and fifty mother-child dyads were analyzed where the mother had high dental caries. Mothers reported perceived social support across four domains (appraisal, tangible, self-esteem, belonging) from the Interpersonal Support Evaluation List instrument (ISEL), with higher scores representing greater support. The association between each social support domain and the probability of high child dental caries was examined. Results: Twenty-seven percent of children (67 out of 250) had high dental caries, and the odds of children having high caries was lower by seven percent for every one point increase in the ISEL appraisal score (odds ratio equals 0.93; 95 percent confidence interval equals 0.88, 0.99). Tangible, self-esteem, and belonging social support ISEL subscales were not significantly associated with high child dental caries (P>0.05). Conclusions: Among mothers with high dental caries, there was modest evidence that appraisal support-the perceived availability of someone to talk to about problems-was associated with lower odds of their children having high dental caries. (Pediatr Dent 2019;41(3):200-5) Received December 2, 2018 | Last Revision April 19, 2019 | Accepted April 22, 2019.