Relationship between bacterial load, morbidity and cagA gene in patients infected by Helicobacter pylori

Belda, Sofía; Sáez, J.; Santibáñez, Miguel; Rodrı́guez, Juan Carlos; Sola-Vera, Javier; Ruiz‐García, Montserrat; Brotons, Alicia; López-Girona, Elena; Pérez, Estefanía; Sillero, C; Royo, Gloria

doi:10.1111/j.1469-0691.2012.03884.x

Cited by 21 publications

(16 citation statements)

References 17 publications

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“…This information has been associated with disease eradication rate, ulcer healing rate, and antral inflammation (15). In addition, our previously reported results showed that upper gastrointestinal bleeding was more closely associated with the bacterial load than the presence of the cagA gene, suggesting the importance of quantifying the bacterial load in order to gain a better understanding of the complex interaction between the microorganism and gastric mucosa (1).…”

Section: Discussionmentioning

confidence: 94%

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Real-Time PCR for Diagnosing Helicobacter pylori Infection in Patients with Upper Gastrointestinal Bleeding: Comparison with Other Classical Diagnostic Methods

et al. 2012

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The aim of this study was to determine the diagnostic usefulness of quantification of the H. pylori genome in detection of infection in patients with upper gastrointestinal bleeding (UGB). A total of 158 consecutive patients with digestive disorders, 80 of whom had clinical presentation of UGB, were studied. The number of microorganisms was quantified using a real-time PCR system which amplifies the urease gene with an internal control for eliminating the false negatives. A biopsy sample from the antrum and corpus of each patient was processed. The rapid urease test, culture, histological study, stool antigen test, and breath test were done. The gold standard was a positive culture or positive results in at least two of the other techniques. When a positive result was defined as any number of microorganisms/human cell, the sensitivity of real-time PCR was greater in bleeding patients, especially in the gastric corpus: 68.4% (95% confidence interval [CI], 52.3 to 84.5%) in non-UGB patients versus 91.5% (95% CI, 79.6 to 97.6%) in UGB patients. When a positive result was defined as a number of microorganisms/human cell above the optimal value that maximizes the Youden index (>3.56 microorganisms/human cell in the antrum and >2.69 in the corpus), the sensitivity and specificity in UGB patients were over 80% in both antrum and corpus. Our findings suggest that some bleeding patients with infection caused by H. pylori may not be correctly diagnosed by classical methods, and such patients could benefit from the improved diagnosis provided by real-time PCR. However, the clinical significance of a small number of microorganisms in patients with negative results in classical tests should be evaluated.

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Section: Discussionmentioning

confidence: 94%

“…The microorganisms were detected using a specific control probe marked with a different fluorochrome (VIC) (see Fig. S1 in the supplemental material) (1). The reaction took place in a real-time PCR 7500 apparatus (Applied Biosystems).…”

Section: Methodsmentioning

confidence: 99%

Real-Time PCR for Diagnosing Helicobacter pylori Infection in Patients with Upper Gastrointestinal Bleeding: Comparison with Other Classical Diagnostic Methods

et al. 2012

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“…We observed a two log range of H. pylori loads in the stool and the load is significantly higher in those with a cagA -positive strain. Density of H. pylori in the stomach also varies among infected individuals, and a higher H. pylori load in the stomach among individuals infected with a cagA -positive strain has been previously reported [41]. The relationship between H. pylori load in the stool and density of infection in the stomach, as well as other possible factors such as level of inflammation, disease state, or bacterial genetic factors, is not presently understood.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Detection and Genotyping of Helicobacter pylori from Stool using Droplet Digital PCR Reveals Variation in Bacterial Loads that Correlates with cagA Virulence Gene Carriage

et al. 2015

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Background Epidemiologic studies of the carcinogenic stomach bacterium Helicobacter pylori have been limited by the lack of non-invasive detection and genotyping methods. We developed a new stool-based method for detection, quantification, and partial genotyping of H. pylori using droplet digital PCR (ddPCR), which allows for increased sensitivity and absolute quantification by PCR partitioning. Materials and Methods Stool-based ddPCR assays for H. pylori 16S gene detection and cagA virulence gene typing were tested using a collection of 50 matched stool and serum samples from Costa Rican volunteers and 29 H. pylori stool antigen-tested stool samples collected at a U.S. hospital. Results The stool-based H. pylori 16S ddPCR assay had a sensitivity of 84% and 100% and a specificity of 100% and 71% compared to serology and stool antigen tests, respectively. The stool-based cagA genotyping assay detected cagA in 22 (88%) of 25 stools from CagA antibody-positive individuals and 4 (16%) of 25 stools from CagA antibody-negative individuals from Costa Rica. All 26 of these samples had a Western-type cagA allele. Presence of serum CagA antibodies was correlated with a significantly higher load of H. pylori in the stool. Conclusions The stool-based ddPCR assays are a sensitive, non-invasive method for detection, quantification, and partial genotyping of H. pylori. The quantitative nature of ddPCR-based H. pylori detection revealed significant variation in bacterial load among individuals that correlates with presence of the cagA virulence gene. These stool-based ddPCR assays will facilitate future population-based epidemiologic studies of this important human pathogen.

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“…A number of studies report that the presence of a factor increases the density of a microbe in experimental hosts, as determined by colony counts for various body sites (Belda et al, 2012;Crotty Alexander et al, 2010;Kasper et al, 2014), that is, they identify proliferation factors. Stp1 is a malevolence factor in that system.…”

Section: Specific Molecular Factorsmentioning

confidence: 99%

Proliferation and benevolence—A framework for dissecting the mechanisms of microbial virulence and health promotion

Waldetoft

Råberg

Lood

2020

Evolutionary Applications

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Key topics in the study of host-microbe interactions-such as the prevention of drug resistance and the exploitation of beneficial effects of bacteria-would benefit from concerted efforts with both mechanistic and evolutionary approaches. But due to differences in intellectual traditions, insights gained in one field rarely benefit the other.Here, we develop a conceptual and analytical framework for the integrated study of host-microbe interactions. This framework partitions the health effects of microbes and the effector molecules they produce into components with different evolutionary implications. It thereby facilitates the prediction of evolutionary responses to inhibition and exploitation of specific molecular mechanisms. | INTRODUC TI ONMicrobes have profound effects on the health of their hosts, and host-microbe interactions are therefore subject to intense research from both mechanistic and evolutionary perspectives. Traditionally pursued in isolation, these lines of inquiry are now becoming increasingly intertwined (Bordenstein & Theis, 2015). This is especially so in the work on antibiotic resistance evolution, and the consequent search for molecular targets for evolution-proof drugs, including antivirulence therapeutics (Allen, Popat, Diggle, & Brown, 2014).Progress is hampered, however, by a lack of common conceptual ground; key concepts in one field, such as "virulence factor" in microbial pathogenesis research (Falkow, 1988(Falkow, , 2004 do not fit into the conceptual structure of the other, for example the trade-off paradigm in virulence evolution theory (Alizon, Hurford, Mideo, & Van Baalen, 2009) (because the former is focused on the mechanisms of host harm, whereas the latter disregards mechanism, and assumes relationships between host harm and pathogen fitness). This is unfortunate because pressing public health challenges, most notably antibiotic resistance, are complex and have several aspects that are studied in both fields.The aim of this paper is to lay a foundation for a common conceptual framework for host-microbe interactions, in which mechanistic and evolutionary traditions can be integrated. To this end, we combine the analytical approach of resistance-tolerance theory in evolutionary ecology (Råberg, Sim, & Read, 2007) with the experimental strategy for identifying virulence factors in microbial pathogenesis research (Falkow, 1988). Whilst most commonly applied to pathogens in acute infections, this type of experiment can identify a range of molecules that impact host health, whether the effect is detrimental or beneficial, the microbe obligate or opportunistic, and the condition acute or chronic. And we intend our analysis to be equally broad. The framework we propose is visual and intuitive, but it also has a simple statistical formalization based on generalized linear models, which makes it flexible and open for further developments.In the main text, we develop the concepts and their implications under the assumption that the microbe's health effect and fitness are linearly relat...

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Relationship between bacterial load, morbidity and cagA gene in patients infected by Helicobacter pylori

Cited by 21 publications

References 17 publications

Real-Time PCR for Diagnosing Helicobacter pylori Infection in Patients with Upper Gastrointestinal Bleeding: Comparison with Other Classical Diagnostic Methods

Real-Time PCR for Diagnosing Helicobacter pylori Infection in Patients with Upper Gastrointestinal Bleeding: Comparison with Other Classical Diagnostic Methods

Quantitative Detection and Genotyping of Helicobacter pylori from Stool using Droplet Digital PCR Reveals Variation in Bacterial Loads that Correlates with cagA Virulence Gene Carriage

Proliferation and benevolence—A framework for dissecting the mechanisms of microbial virulence and health promotion

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