FdeC expression regulates motility and adhesion of the avian pathogenic Escherichia coli strain IMT5155.

Adaptation of avian pathogenic E. coli (APEC) to changing host environments including virulence factors expression is vital for disease progression. FdeC is an autotransporter adhesin that plays a role in uropathogenic Escherichia coli (UPEC) adhesion to epithelial cells. Expression of fdeC is known to be regulated by environmental conditions in UPEC and Shiga toxin-producing E. coli (STEC). The observation in a previous study that an APEC strain IMT5155 in which the fdeC gene was disrupted by a transposon insertion resulted in elevated adhesion to chicken intestinal cells prompted us to further explore the role of fdeC in infection. We found that the fdeC gene prevalence and FdeC variant prevalence differed between APEC and nonpathogenic E. coli genomes. Expression of the fdeC gene was induced at host body temperature, an infection relevant condition. Disruption of fdeC resulted in greater adhesion to CHIC-8E11 cells and increased motility at 42 °C compared to wild type (WT) and higher expression of multiple transporter proteins that increased inorganic ion export. Increased motility may be related to increased inorganic ion export since this resulted in downregulation of YbjN, a protein known to supress motility. Inactivation of fdeC in APEC strain IMT5155 resulted in a weaker immune response in chickens compared to WT in experimental infections. Our findings suggest that FdeC is upregulated in the host and contributes to interactions with the host by down-modulating motility during colonization. A thorough understanding of the regulation and function of FdeC could provide novel insights into E. coli pathogenesis.

It takes two to attach - endo-1,3-ß-d-glucanase as a potential receptor of mannose-independent, FimH-dependent Salmonella Typhimurium binding to spinach leaves.

Currently, fresh, unprocessed food has become a relevant element of the chain of transmission of enteropathogenic infections. To survive on a plant surface and further spread the infections, pathogens like Salmonella have to attach stably to the leaf surface. Adhesion, driven by various virulence factors, including the most abundant fim operon encoding type 1 fimbriae, is usually an initial step of infection, preventing physical removal of the pathogen. Adhesion properties of Salmonella's type 1 fimbriae and its FimH adhesin were investigated intensively in the past. However, there is a lack of knowledge regarding its role in interaction with plant cells. Understanding the mechanisms and structures involved in such interaction may facilitate efforts to decrease the risk of contamination and increase fresh food safety. Here, we applied Salmonella genome site-directed mutagenesis, adhesion assays, protein-protein interactions, and biophysics methods based on surface plasmon resonance to unravel the role of FimH adhesin in interaction with spinach leaves. We show that FimH is at least partially responsible for Salmonella binding to spinach leaves, and this interaction occurs in a mannose-independent manner. Importantly, we identified a potential FimH receptor as endo-1,3-ß-d-Glucanase and found that this interaction is strong and specific, with a dissociation constant in the nanomolar range. This research advances our comprehension of Salmonella's interactions with plant surfaces, offering insights that can aid in minimizing contamination risks and improving the safety of fresh, unprocessed foods.

A randomized controlled trial on COGITO, a free self-help smartphone app to enhance mental well-being.

BACKGROUND: Smartphone apps may help to prevent the transition from minor to severe mental health problems. We compared a free self-help smartphone app (COGITO; www.uke.de/cogito_app) against a wait-list condition for the improvement of self-esteem and depression. METHODS: The Rosenberg Self-Esteem Scale represented the primary outcome in this controlled trial. The final sample (n = 213) was randomly assigned to either the app or to the control condition. RESULTS: The app condition significantly improved the primary outcome relative to controls for all analyses. Satisfaction of completers was high. The present results warrant independent replication; the retention rate needs to be increased to allow solid inferences about acceptance. CONCLUSIONS: The present study demonstrates that the COGITO app may represent an effective self-help tool for psychological problems.

Characterization of clumpy adhesion of Escherichia coli to human cells and associated factors influencing antibiotic sensitivity.

Escherichia coli intestinal infection pathotypes are characterized by distinct adhesion patterns, including the recently described clumpy adhesion phenotype. Here, we identify and characterize the genetic factors contributing to the clumpy adhesion of E. coli strain 4972. In this strain, the transcriptome and proteome of adhered bacteria were found to be distinct from planktonic bacteria in the supernatant. A total of 622 genes in the transcriptome were differentially expressed in bacteria present in clumps relative to the planktonic bacteria. Seven genes targeted for disruption had variable distribution in different pathotypes and nonpathogenic E. coli, with the pilV and spnT genes being the least frequent or absent from most groups. Deletion (Δ) of five differentially expressed genes, flgH, ffp, pilV, spnT, and yggT, affected motility, adhesion, or antibiotic stress. ΔflgH exhibited 80% decrease and ΔyggT depicted 184% increase in adhesion, and upon complementation, adhesion was significantly reduced to 13%. ΔflgH lost motility and was regenerated when complemented, whereas Δffp had significantly increased motility, and reintroduction of the same gene reduced it to the wild-type level. The clumps produced by Δffp and ΔspnT were more resistant and protected the bacteria, with ΔspnT showing the best clump formation in terms of ampicillin stress protection. ΔyggT had the lowest tolerance to gentamicin, where the antibiotic stress completely eliminated the bacteria. Overall, we were able to investigate the influence of clump formation on cell surface adhesion and antimicrobial tolerance, with the contribution of several factors crucial to clump formation on susceptibility to the selected antibiotics. IMPORTANCE: The study explores a biofilm-like clumpy adhesion phenotype in Escherichia coli, along with various factors and implications for antibiotic susceptibility. The phenotype permitted the bacteria to survive the onslaught of high antibiotic concentrations. Profiles of the transcriptome and proteome allowed the differentiation between adhered bacteria in clumps and planktonic bacteria in the supernatant. The deletion mutants of genes differentially expressed between adhered and planktonic bacteria, i.e., flgH, ffp, pilV, spnT, and yggT, and respective complementations in trans cemented their roles in multiple capacities. ffp, an uncharacterized gene, is involved in motility and resistance to ampicillin in a clumpy state. The work also affirms for the first time the role of the yggT gene in adhesion and its involvement in susceptibility against another aminoglycoside antibiotic, i.e., gentamicin. Overall, the study contributes to the mechanisms of biofilm-like adhesion phenotype and understanding of the antimicrobial therapy failures and infections of E. coli.

A systematic review of performance-based assessment studies on cognitive biases in schizophrenia spectrum psychoses and clinical high-risk states: A summary of 40 years of research.

Cognitive models of psychosis have stimulated empirical studies on cognitive biases involved in schizophrenia spectrum psychoses and their symptoms. This systematic review aimed to summarize the studies on the role of cognitive biases as assessed in different performance-based tasks in schizophrenia spectrum psychoses and clinical high-risk states. We focused on five cognitive biases linked to psychosis, i.e., aberrant salience, attentional biases, source monitoring biases, jumping to conclusions, and bias against disconfirmatory evidence. We identified N = 324 studies published in N = 308 articles fulfilling inclusion criteria. Most studies have been cross-sectional and confirmed that the schizophrenia spectrum psychoses are related to exaggerated cognitive biases compared to healthy controls. On the contrary, less evidence suggests a higher tendency for cognitive biases in the UHR sample. The only exceptions were source monitoring and jumping to conclusions, which were confirmed to be exaggerated in both clinical groups. Hallucinations and delusions were the most frequent symptoms studied in the context of cognitive biases. Based on the findings, we presented a hypothetical model on the role of interactions between cognitive biases or additive effects of biases in shaping the risk of psychosis. Future research is warranted for further development of cognitive models for psychosis.

Assessing psychotic-like experiences using categorical and metacognitive approaches: A validation of polish self-report measures.

AIM: Psychotic-like experiences (PLEs) are experiences in the general population that, in their extreme form, are attributed to clinical psychosis. They are correlated with general psychopathology and increased risk of developing psychosis. Previous research show a multitude of measuring tools which most often lack psychometric validation. This study aimed to examine both categorical and metacognitive measures of PLEs. METHODS: Confirmatory Factor Analysis (CFA) was used in seven online studies with n's ranging from 259 to 6772 to explore factor structures of Prodromal Questionnaire 16 item (PQ-16), Revised Green et al. Paranoid Thoughts Scale (R-GPTS), Multi-Modality Unusual Sensory Experiences Questionnaire (MUSEQ), Beliefs about Paranoia Scale (BAPS) and Interpretation of Voices Inventory (IVI). Additionally, we explored measurement invariance between diagnosed with psychiatric disorders and undiagnosed individuals in PQ-16, R-GPTS and BAPS. RESULTS: We confirmed the factor structures of all questionnaires except IVI. We confirmed configural, threshold and metric measurement invariance in R-GPTS and BAPS and partially PQ-16. CONCLUSIONS: The current results demonstrate structural validity and measurement invariance of several categorical and metacognitive measures of PLEs.

What Kurt Schneider Really Said and What the DSM Has Made of it in Its Different Editions: A Plea to Redefine Hallucinations in Schizophrenia.

Kurt Schneider has played a leading role in shaping our current view of schizophrenia, placing certain manifestations of delusions and hallucinations at the center of the disorder, especially ideas of persecution and voice-hearing. The first part of this review summarizes Schneider's original ideas and then traces how the different editions of the DSM merged aspects of Kraepelin's, Bleuler's, and Schneider's historical concepts. Special attention is given to the transition from the DSM-IV to the DSM-5, which eliminated much of Schneider's original concept. In the second part of the article, we contrast the current definition of hallucination in the DSM-5 with that of Schneider. We present empirically derived arguments that favor a redefinition of hallucinations, much in accordance with Schneider's original ideas. We plea for a two-dimensional model of hallucinations that represents the degree of insight and perceptuality, ranging from thoughts with full "mineness" via perception-laden thoughts and intrusions (including "as if" experiences") to hallucinations. While we concur with the DSM-5 that cognitions that are indistinguishable from perceptions should be labeled as hallucinations, we suggest expanding the definition to internally generated sensory phenomena, including those with only partial resemblance to external perceptions, that the individual considers real and that may lie at the heart of a subsequent delusional superstructure.

Prevalence of body-focused repetitive behaviors in a diverse population sample - rates across age, gender, race and education.

BACKGROUND: Prevalence estimates for body-focused repetitive behaviors (BFRBs) such as trichotillomania differ greatly across studies owing to several confounding factors (e.g. different criteria). For the present study, we recruited a diverse online sample to provide estimates for nine subtypes of BFRBs and body-focused repetitive disorders (BFRDs). METHODS: The final sample comprised 1481 individuals from the general population. Several precautions were taken to recruit a diverse sample and to exclude participants with low reliability. We matched participants on gender, race, education and age range to allow unbiased interpretation. RESULTS: While almost all participants acknowledged at least one BFRB in their lifetime (97.1%), the rate for BFRDs was 24%. Nail biting (11.4%), dermatophagia (8.7%), skin picking (8.2%), and lip-cheek biting (7.9%) were the most frequent BFRDs. Whereas men showed more lifetime BFRBs, the rate of BFRDs was higher in women than in men. Rates of BFRDs were low in older participants, especially after the age of 40. Overall, BFRBs and BFRDs were more prevalent in White than in non-White individuals. Education did not show a strong association with BFRB/BFRDs. DISCUSSION: BFRBs are ubiquitous. More severe forms, BFRDs, manifest in approximately one out of four people. In view of the often-irreversible somatic sequelae (e.g. scars) BFRBs/BFRDs deserve greater diagnostic and therapeutic attention by clinicians working in both psychology/psychiatry and somatic medicine (especially dermatology and dentistry).

Salmonella adhesion is decreased by hypoxia due to adhesion and motility structure crosstalk.

Initial stages of Salmonella Typhimurium infection involve a series of coordinated events aimed at reaching, attaching to, and invading host cells. Virulence factors such as flagella, fimbriae, and secretion systems play crucial roles in these events and are regulated in response to the host environment. The first point of contact between the pathogen and host is the intestinal epithelial layer, which normally serves as a barrier against invading pathogens, but can also be an entry site for pathogens. The integrity of this barrier can be modulated by the hypoxic environment of the intestines, created by the presence of trillions of microbes. Variable oxygen concentrations can strongly affect many functions of the gut, including secretion of cytokines and growth factors from the host site and affect the ability of Salmonella to persist, invade, and replicate. In this study, we investigated the first stages of Salmonella Typhimurium infection under hypoxic conditions in vitro and found that low oxygen levels significantly decreased bacterial adhesion. Using adhesion and motility assays, biofilm formation tests, as well as gene expression and cytokine secretion analysis, we identified a hypoxia-specific cross-talk between the expression of type 1 fimbriae and flagella, suggesting that altered flagellin expression levels affect the motility of bacteria and further impact their adhesion level, biofilm formation ability, and innate immune response. Overall, understanding how Salmonella interacts with its variable host environment provides insights into the virulence mechanisms of the bacterium and information regarding strategies for preventing or treating infections. Further research is required to fully understand the complex interplay between Salmonella and its host environment.

Cognitive correlates of auditory hallucinations in schizophrenia spectrum disorders.

Auditory hallucinations (AHs) are one of the central symptoms of schizophrenia spectrum disorders (SSD). Current cognitive models of AH implicate source monitoring, top-down processes, and inhibitory control. However, research combining these processes is limited. Our study aimed to examine how source monitoring bias, top-down processes, and inhibitory control contribute to AHs in individuals with SSD. Eighty seven patients (aged 18-45 years) with SSD were included in the analyses. Participants completed cognitive tasks assessing source monitoring (Action Memory Task), top-down processes (False Perception Task; FPT), and inhibitory control (Auditory Go/NoGo task). AH was positively associated with response bias on the FPT. Correlations between AH and the other cognitive tasks were nonsignificant. Source monitoring errors correlated positively with response bias measures and negatively with Hits on the FPT. PANSS total score was positively correlated with source monitoring bias and False Alarms on the Go/NoGo task. The severity of disorganized symptoms was related to Source Monitoring Errors and False Alarms in the Go/NoGo task. Negative symptoms were associated with Hits and False Alarms in the Go/NoGo task. Future studies are necessary to further elucidate the relationships between different cognitive processes that may be related to clinical symptoms of psychosis.

Hasty decision making and belief inflexibility in the more delusion prone? A modified disambiguating-scenarios paradigm assessing cognitive biases implicated in delusions.

INTRODUCTION: Contemporary models of psychosis imply that cognitive biases such as the jumping to conclusions (JTC), the bias against disconfirmatory evidence (BADE), and the liberal acceptance (LA) bias play a role in the pathogenesis of delusions. Most of the studies investigating the role of cognitive biases, however, have been conducted with socially neutral or abstract stimuli and have assessed patients with established psychoses. For the present study, we aimed to concurrently investigate multiple biases (i.e., the JTC, BADE, and LA biases) in a community sample with a new paradigm using more socially engaging stimuli. METHODS: A large sample of participants (N = 874) recruited via Amazon Mechanical Turk was subdivided into two groups based on the frequency of their psychotic-like experiences (PLEs) according to the positive subscale score of the Community Assessment of Psychic Experiences (CAPE) and matched based on major demographics variables, resulting in two equally sized groups called High-PLE (at least 2 SD above the mean) and Low-PLE (maximum 0.5 above the mean; n = 46 for each group). Using a modified version of the written-scenarios BADE task, which emphasized social interactions between agents embedded in the scenario, participants rated the plausibility of response options in the face of new information. RESULTS: In line with previous findings, the High-PLE group demonstrated the JTC, BADE, and LA biases. That is, the members of this group made more decisions after the initial piece of information, were less likely to revise their beliefs in light of new information, and provided higher plausibility ratings for implausible response options compared to the Low-PLE group. CONCLUSIONS: Results corroborate prior findings suggesting that the JTC, BADE, and LA biases may be contributing factors in delusional ideation and that metacognitive biases extend to social situations.

Better together-Salmonella biofilm-associated antibiotic resistance.

Salmonella poses a serious threat to public health and socioeconomic development worldwide because of its foodborne pathogenicity and antimicrobial resistance. This biofilm-planktonic lifestyle enables Salmonella to interfere with the host and become resistant to drugs, conferring inherent tolerance to antibiotics. The complex biofilm structure makes bacteria tolerant to harsh conditions due to the diversity of physiological, biochemical, environmental, and molecular factors constituting resistance mechanisms. Here, we provide an overview of the mechanisms of Salmonella biofilm formation and antibiotic resistance, with an emphasis on less-studied molecular factors and in-depth analysis of the latest knowledge about upregulated drug-resistance-associated genes in bacterial aggregates. We classified and extensively discussed each group of these genes encoding transporters, outer membrane proteins, enzymes, multiple resistance, metabolism, and stress response-associated proteins. Finally, we highlighted the missing information and studies that need to be undertaken to understand biofilm features and contribute to eliminating antibiotic-resistant and health-threatening biofilms.

Genomic characterization of enterohaemolysin-encoding haemolytic Escherichia coli of animal and human origin.

Enterohaemolysin (Ehx) and alpha-haemolysin are virulence-associated factors (VAFs) causing the haemolytic phenotype in Escherichia coli. It has been shown that chromosomally and plasmid-encoded alpha-haemolysin are characteristic of specific pathotypes, virulence-associated factors and hosts. However, the prevalence of alpha- and enterohaemolysin does not overlap in the majority of pathotypes. Therefore, this study focuses on the characterization of the haemolytic E. coli population associated with multiple pathotypes in human and animal infectious diseases. Using a genomics approach, we investigated characteristic features of the enterohaemolysin-encoding strains to identify factors differentiating enterohaemolysin-positive from alpha-haemolysin-positive E. coli populations. To shed light on the functionality of Ehx subtypes, we analysed Ehx-coding genes and inferred EhxA phylogeny. The two haemolysins are associated with a different repertoire of adhesins, iron acquisition or toxin systems. Alpha-haemolysin is predominantly found in uropathogenic E. coli (UPEC) and predicted to be chromosomally encoded, or nonpathogenic and undetermined E. coli pathotypes and typically predicted to be plasmid-encoded. Enterohaemolysin is mainly associated with Shiga toxin-producing E. coli (STEC) and enterohaemorrhagic E. coli (EHEC) and predicted to be plasmid-encoded. Both types of haemolysin are found in atypical enteropathogenic E. coli (aEPEC). Moreover, we identified a new EhxA subtype present exclusively in genomes with VAFs characteristic of nonpathogenic E. coli. This study reveals a complex relationship between haemolytic E. coli of diverse pathotypes, providing a framework for understanding the potential role of haemolysin in pathogenesis.

Phantom phone signals and other hallucinatory-like experiences: Investigation of similarities and differences.

Phantom Phone Signals (PPS) and other hallucinatory-like experiences (HLEs) are perceptual anomalies that are commonly reported in the general population. Both phenomena concern the same sensory modality, but PPS are restricted to smartphone use. The current study aimed to assess similarities and differences between these types of anomalies in relation to general psychopathology, metacognitive beliefs about perception, smartphone dependence, and susceptibility to top-down influences on perception. We analyzed data from a Polish community sample (N = 236, aged 18-69). We used questions pertaining to PPS, a questionnaire pertaining to HLEs (Multi-Modality Unusual Sensory Experiences Questionnaire), and other variables of interest (Symptom Checklist-27-plus, Mobile Phone Problematic Use Scale, and the Beliefs about Perception Questionnaire). Additionally, a false-perception task manipulating cognitive expectancy (i.e., a visual cue associated with auditory stimuli vs. no visual cue) was devised to measure top-down influences on perception. Regression analyses showed that only top-down beliefs about perception predicted both PPS and HLEs. Smartphone dependency proved to be a stronger predictor of PPS than other measured variables, whereas for HLEs, general psychopathology was the strongest predictor. Current results suggest that despite sharing some mechanisms, PPS and HLEs may have independent underlying factors.

Membrane properties modulation by SanA: implications for xenobiotic resistance in Salmonella Typhimurium.

Introduction: Multidrug resistance in bacteria is a pressing concern, particularly among clinical isolates. Gram-negative bacteria like Salmonella employ various strategies, such as altering membrane properties, to resist treatment. Their two-membrane structure affects susceptibility to antibiotics, whereas specific proteins and the peptidoglycan layer maintain envelope integrity. Disruptions can compromise stability and resistance profile toward xenobiotics. In this study, we investigated the unexplored protein SanA's role in modifying bacterial membranes, impacting antibiotic resistance, and intracellular replication within host cells. Methods: We generated a sanA deletion mutant and complemented it in trans to assess its biological function. High-throughput phenotypic profiling with Biolog Phenotype microarrays was conducted using 240 xenobiotics. Membrane properties and permeability were analyzed via cytochrome c binding, hexadecane adhesion, nile red, and ethidium bromide uptake assays, respectively. For intracellular replication analysis, primary bone marrow macrophages served as a host cells model. Results: Our findings demonstrated that the absence of sanA increased membrane permeability, hydrophilicity, and positive charge, resulting in enhanced resistance to certain antibiotics that target peptidoglycan synthesis. Furthermore, the sanA deletion mutant demonstrated enhanced replication rates within primary macrophages, highlighting its ability to evade the bactericidal effects of the immune system. Taking together, we provide valuable insights into a poorly known SanA protein, highlighting the complex interplay among bacterial genetics, membrane physiology, and antibiotic resistance, underscoring its significance in understanding Salmonella pathogenicity.

Genome placement of alpha-haemolysin cluster is associated with alpha-haemolysin sequence variation, adhesin and iron acquisition factor profile of Escherichia coli.

Since the discovery of haemolysis, many studies focused on a deeper understanding of this phenotype in Escherichia coli and its association with other virulence genes, diseases and pathogenic attributes/functions in the host. Our virulence-associated factor profiling and genome-wide association analysis of genomes of haemolytic and nonhaemolytic E. coli unveiled high prevalence of adhesins, iron acquisition genes and toxins in haemolytic bacteria. In the case of fimbriae with high prevalence, we analysed sequence variation of FimH, EcpD and CsgA, and showed that different adhesin variants were present in the analysed groups, indicating altered adhesive capabilities of haemolytic and nonhaemolytic E. coli. Analysis of over 1000 haemolytic E. coli genomes revealed that they are pathotypically, genetically and antigenically diverse, but their adhesin and iron acquisition repertoire is associated with genome placement of hlyCABD cluster. Haemolytic E. coli with chromosome-encoded alpha-haemolysin had high frequency of P, S, Auf fimbriae and multiple iron acquisition systems such as aerobactin, yersiniabactin, salmochelin, Fec, Sit, Bfd and hemin uptake systems. Haemolytic E. coli with plasmid-encoded alpha-haemolysin had similar adhesin profile to nonpathogenic E. coli, with high prevalence of Stg, Yra, Ygi, Ycb, Ybg, Ycf, Sfm, F9 fimbriae, Paa, Lda, intimin and type 3 secretion system encoding genes. Analysis of HlyCABD sequence variation revealed presence of variants associated with genome placement and pathotype.

Neural Correlates of Aberrant Salience and Source Monitoring in Schizophrenia and At-Risk Mental States-A Systematic Review of fMRI Studies.

Cognitive biases are an important factor contributing to the development and symptom severity of psychosis. Despite the fact that various cognitive biases are contributing to psychosis, they are rarely investigated together. In the current systematic review, we aimed at investigating specific and shared functional neural correlates of two important cognitive biases: aberrant salience and source monitoring. We conducted a systematic search of fMRI studies of said cognitive biases. Eight studies on aberrant salience and eleven studies on source monitoring were included in the review. We critically discussed behavioural and neuroimaging findings concerning cognitive biases. Various brain regions are associated with aberrant salience and source monitoring in individuals with schizophrenia and the risk of psychosis. The ventral striatum and insula contribute to aberrant salience. The medial prefrontal cortex, superior and middle temporal gyrus contribute to source monitoring. The anterior cingulate cortex and hippocampus contribute to both cognitive biases, constituting a neural overlap. Our review indicates that aberrant salience and source monitoring may share neural mechanisms, suggesting their joint role in producing disrupted external attributions of perceptual and cognitive experiences, thus elucidating their role in positive symptoms of psychosis. Account bridging mechanisms of these two biases is discussed. Further studies are warranted.

Whatever makes them stick - Adhesins of avian pathogenic Escherichia coli.

Avian pathogenic Escherichia coli (APEC) is associated with extraintestinal infections and the development of colibacillosis, causing high mortality in farm birds and extensive losses in the poultry industry worldwide. The virulence of APEC is a complex phenomenon associated with numerous mechanisms involving a variety of extracellular and intracellular structures to overcome host barriers. Initial bacterial attachment or adhesion to host cells is vital to bacterial pathogenesis and is determined by various adhesins. These proteins protect pathogens against possible host defense mechanisms, enabling the effective use of other virulence attributes. Considering this property, the current review provides a systematic and in-depth analysis of the latest information on adhesins analyzed in APEC strains. This review discusses in detail each of the adhesin types, such as fimbrial chaperone-usher, fimbrial curli, nonfimbrial and atypical adhesins, and their components, presenting an opportunity to gain a better understanding of different adhesins and mechanisms employed in pathogenesis. Additionally, the article scrutinizes and notes missing information and potential studies that need to be undertaken to develop a complete understanding of APEC adhesion.

Identification of Natural Mutations Responsible for Altered Infection Phenotypes of Salmonella enterica Clinical Isolates by Using Cell Line Infection Screens.

The initial steps of Salmonella pathogenesis involve adhesion to and invasion into host epithelial cells. While well-studied for Salmonella enterica serovar Typhimurium, the factors contributing to this process in other, host-adapted serovars remains unexplored. Here, we screened clinical isolates of serovars Gallinarum, Dublin, Choleraesuis, Typhimurium, and Enteritidis for adhesion to and invasion into intestinal epithelial cell lines of human, porcine, and chicken origins. Thirty isolates with altered infectivity were used for genomic analyses, and 14 genes and novel mutations associated with high or low infectivity were identified. The functions of candidate genes included virulence gene expression regulation and cell wall or membrane synthesis and components. The role of several of these genes in Salmonella adhesion to and invasion into cells has not previously been investigated. The genes dksA (encoding a stringent response regulator) and sanA (encoding a vancomycin high-temperature exclusion protein) were selected for further analyses, and we confirmed their roles in adhesion to and invasion into host cells. Furthermore, transcriptomic analyses were performed for S Enteritidis and S Typhimurium, with two highly infective and two marginally infective isolates for each serovar. Expression profiles for the isolates with altered infection phenotypes revealed the importance of type 3 secretion system expression levels in the determination of an isolate's infection phenotype. Taken together, these data indicate a new role in cell host infection for genes or gene variants previously not associated with adhesion to and invasion into the epithelial cells.IMPORTANCESalmonella is a foodborne pathogen affecting over 200 million people and resulting in over 200,000 fatal cases per year. Its adhesion to and invasion into intestinal epithelial cells represent one of the first and key steps in the pathogenesis of salmonellosis. Still, around 35 to 40% of bacterial genes have no experimentally validated function, and their contribution to bacterial virulence, including adhesion and invasion, remains largely unknown. Therefore, the significance of this study is in the identification of new genes or gene allelic variants previously not associated with adhesion and invasion. It is well established that blocking adhesion and/or invasion would stop or hamper bacterial infection; therefore, the new findings from this study could be used in future developments of anti-Salmonella therapy targeting genes involved in these key processes. Such treatment could be a valuable alternative, as the prevalence of antibiotic-resistant bacteria is increasing very rapidly.