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Microbiology Spectrum Jun 2016Pertussis is a highly infectious vaccine-preventable cough illness that continues to be a significant source of morbidity and mortality around the world. The majority of... (Review)
Review
Pertussis is a highly infectious vaccine-preventable cough illness that continues to be a significant source of morbidity and mortality around the world. The majority of human illness is caused by Bordetella pertussis, and some is caused by Bordetella parapertussis. Bordetella is a Gram-negative, pleomorphic, aerobic coccobacillus. In the past several years, even countries with high immunization rates in early childhood have experienced rises in pertussis cases. Reasons for the resurgence of reported pertussis may include molecular changes in the organism and increased awareness and diagnostic capabilities, as well as lessened vaccine efficacy and waning immunity. The most morbidity and mortality with pertussis infection is seen in infants too young to benefit from immunization. Severe infection requiring hospitalization, including in an intensive care setting, is mostly seen in those under 3 months of age. As a result, research and public health actions have been aimed at better understanding and reducing the spread of Bordetella pertussis. Studies comparing the cost benefit of cocooning strategies versus immunization of pregnant women have been favorable towards immunizing pregnant women. This strategy is expected to prevent a larger number of pertussis cases, hospitalizations, and deaths in infants <1 year old while also being cost-effective. Studies have demonstrated that the source of infection in infants usually is a family member. Efforts to immunize children and adults, in particular pregnant women, need to remain strong.
Topics: Anti-Bacterial Agents; Bordetella pertussis; Humans; Infant; Infant, Newborn; Pertussis Vaccine; Vaccination; Whooping Cough
PubMed: 27337481
DOI: 10.1128/microbiolspec.EI10-0008-2015 -
Virulence Dec 2021The highly contagious whooping cough agent has evolved as a human-restricted pathogen from a progenitor which also gave rise to and . While the latter colonizes a... (Review)
Review
The highly contagious whooping cough agent has evolved as a human-restricted pathogen from a progenitor which also gave rise to and . While the latter colonizes a broad range of mammals and is able to survive in the environment, has lost its ability to survive outside its host through massive genome decay. Instead, it has become a highly successful human pathogen by the acquisition of tightly regulated virulence factors and evolutionary adaptation of its metabolism to its particular niche. By the deployment of an arsenal of highly sophisticated virulence factors it overcomes many of the innate immune defenses. It also interferes with vaccine-induced adaptive immunity by various mechanisms. Here, we review data from , human and animal models to illustrate the mechanisms of adaptation to the human respiratory tract and provide evidence of ongoing evolutionary adaptation as a highly successful human pathogen.
Topics: Animals; Bordetella bronchiseptica; Bordetella parapertussis; Bordetella pertussis; Humans; Mammals; Virulence; Virulence Factors
PubMed: 34590541
DOI: 10.1080/21505594.2021.1980987 -
Nature Reviews. Microbiology Jan 2021Antibiotic-resistant bacterial infections arising from acquired resistance and/or through biofilm formation necessitate the development of innovative 'outside of the... (Review)
Review
Antibiotic-resistant bacterial infections arising from acquired resistance and/or through biofilm formation necessitate the development of innovative 'outside of the box' therapeutics. Nanomaterial-based therapies are promising tools to combat bacterial infections that are difficult to treat, featuring the capacity to evade existing mechanisms associated with acquired drug resistance. In addition, the unique size and physical properties of nanomaterials give them the capability to target biofilms, overcoming recalcitrant infections. In this Review, we highlight the general mechanisms by which nanomaterials can be used to target bacterial infections associated with acquired antibiotic resistance and biofilms. We emphasize design elements and properties of nanomaterials that can be engineered to enhance potency. Lastly, we present recent progress and remaining challenges for widespread clinical implementation of nanomaterials as antimicrobial therapeutics.
Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Biofilms; Coinfection; Drug Carriers; Drug Discovery; Drug Resistance, Bacterial; Humans; Nanostructures; Translational Research, Biomedical
PubMed: 32814862
DOI: 10.1038/s41579-020-0420-1 -
The Lancet. Microbe Mar 2023Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global threat, but the distribution and clinical significance of carbapenemases are unclear. The aim of this... (Observational Study)
Observational Study
BACKGROUND
Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global threat, but the distribution and clinical significance of carbapenemases are unclear. The aim of this study was to define characteristics and outcomes of CRPA infections and the global frequency and clinical impact of carbapenemases harboured by CRPA.
METHODS
We conducted an observational, prospective cohort study of CRPA isolated from bloodstream, respiratory, urine, or wound cultures of patients at 44 hospitals (10 countries) between Dec 1, 2018, and Nov 30, 2019. Clinical data were abstracted from health records and CRPA isolates were whole-genome sequenced. The primary outcome was 30-day mortality from the day the index culture was collected. We compared outcomes of patients with CRPA infections by infection type and across geographic regions and performed an inverse probability weighted analysis to assess the association between carbapenemase production and 30-day mortality.
FINDINGS
We enrolled 972 patients (USA n=527, China n=171, south and central America n=127, Middle East n=91, Australia and Singapore n=56), of whom 581 (60%) had CRPA infections. 30-day mortality differed by infection type (bloodstream 21 [30%] of 69, respiratory 69 [19%] of 358, wound nine [14%] of 66, urine six [7%] of 88; p=0·0012) and geographical region (Middle East 15 [29%] of 52, south and central America 20 [27%] of 73, USA 60 [19%] of 308, Australia and Singapore three [11%] of 28, China seven [6%] of 120; p=0·0002). Prevalence of carbapenemase genes among CRPA isolates also varied by region (south and central America 88 [69%] of 127, Australia and Singapore 32 [57%] of 56, China 54 [32%] of 171, Middle East 27 [30%] of 91, USA ten [2%] of 527; p<0·0001). KPC-2 (n=103 [49%]) and VIM-2 (n=75 [36%]) were the most common carbapenemases in 211 carbapenemase-producing isolates. After excluding USA patients, because few US isolates had carbapenemases, patients with carbapenemase-producing CRPA infections had higher 30-day mortality than those with non-carbapenemase-producing CRPA infections in both unadjusted (26 [22%] of 120 vs 19 [12%] of 153; difference 9%, 95% CI 3-16) and adjusted (difference 7%, 95% CI 1-14) analyses.
INTERPRETATION
The emergence of different carbapenemases among CRPA isolates in different geographical regions and the increased mortality associated with carbapenemase-producing CRPA infections highlight the therapeutic challenges posed by these organisms.
FUNDING
National Institutes of Health.
Topics: United States; Humans; Anti-Bacterial Agents; Pseudomonas aeruginosa; Prospective Studies; Pseudomonas Infections; Carbapenems
PubMed: 36774938
DOI: 10.1016/S2666-5247(22)00329-9 -
Nature Communications May 2019Small intestinal bacterial overgrowth (SIBO) has been implicated in symptoms associated with functional gastrointestinal disorders (FGIDs), though mechanisms remain... (Clinical Trial)
Clinical Trial
Small intestinal bacterial overgrowth (SIBO) has been implicated in symptoms associated with functional gastrointestinal disorders (FGIDs), though mechanisms remain poorly defined and treatment involves non-specific antibiotics. Here we show that SIBO based on duodenal aspirate culture reflects an overgrowth of anaerobes, does not correspond with patient symptoms, and may be a result of dietary preferences. Small intestinal microbial composition, on the other hand, is significantly altered in symptomatic patients and does not correspond with aspirate culture results. In a pilot interventional study we found that switching from a high fiber diet to a low fiber, high simple sugar diet triggered FGID-related symptoms and decreased small intestinal microbial diversity while increasing small intestinal permeability. Our findings demonstrate that characterizing small intestinal microbiomes in patients with gastrointestinal symptoms may allow a more targeted antibacterial or a diet-based approach to treatment.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; DNA, Bacterial; Dietary Fiber; Dietary Sugars; Dysbiosis; Female; Gastrointestinal Diseases; Gastrointestinal Microbiome; Healthy Volunteers; Humans; Intestinal Mucosa; Intestine, Small; Male; Middle Aged; Permeability; Pilot Projects; Young Adult
PubMed: 31043597
DOI: 10.1038/s41467-019-09964-7 -
The Lancet. Infectious Diseases Mar 2022Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a global threat. We therefore analysed the bacterial characteristics of CRKP infections and the clinical outcomes of...
Clinical outcomes and bacterial characteristics of carbapenem-resistant Klebsiella pneumoniae complex among patients from different global regions (CRACKLE-2): a prospective, multicentre, cohort study.
BACKGROUND
Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a global threat. We therefore analysed the bacterial characteristics of CRKP infections and the clinical outcomes of patients with CRKP infections across different countries.
METHODS
In this prospective, multicentre, cohort study (CRACKLE-2), hospitalised patients with cultures positive for CRKP were recruited from 71 hospitals in Argentina, Australia, Chile, China, Colombia, Lebanon, Singapore, and the USA. The first culture positive for CRKP was included for each unique patient. Clinical data on post-hospitalisation death and readmission were collected from health records, and whole genome sequencing was done on all isolates. The primary outcome was a desirability of outcome ranking at 30 days after the index culture, and, along with bacterial characteristics and 30-day all-cause mortality (a key secondary outcome), was compared between patients from China, South America, and the USA. The desirability of outcome ranking was adjusted for location before admission, Charlson comorbidity index, age at culture, Pitt bacteremia score, and anatomical culture source through inverse probability weighting; mortality was adjusted for the same confounders, plus region where relevant, through multivariable logistic regression. This study is registered at ClinicalTrials.gov, NCT03646227, and is complete.
FINDINGS
Between June 13, 2017, and Nov 30, 2018, 991 patients were enrolled, of whom 502 (51%) met the criteria for CRKP infection and 489 (49%) had positive cultures that were considered colonisation. We observed little intra-country genetic variation in CRKP. Infected patients from the USA were more acutely ill than were patients from China or South America (median Pitt bacteremia score 3 [IQR 2-6] vs 2 [0-4] vs 2 [0-4]) and had more comorbidities (median Charlson comorbidity index 3 [IQR 2-5] vs 1 [0-3] vs 1 [0-2]). Adjusted desirability of outcome ranking outcomes were similar in infected patients from China (n=246), South America (n=109), and the USA (n=130); the estimates were 53% (95% CI 42-65) for China versus South America, 50% (41-61) for the USA versus China, and 53% (41-66) for the USA versus South America. In patients with CRKP infections, unadjusted 30-day mortality was lower in China (12%, 95% CI 8-16; 29 of 246) than in the USA (23%, 16-30; 30 of 130) and South America (28%, 20-37; 31 of 109). Adjusted 30-day all-cause mortality was higher in South America than in China (adjusted odds ratio [aOR] 4·82, 95% CI 2·22-10·50) and the USA (aOR 3·34, 1·50-7·47), with the mortality difference between the USA and China no longer being significant (aOR 1·44, 0·70-2·96).
INTERPRETATION
Global CRKP epidemics have important regional differences in patients' baseline characteristics and clinical outcomes, and in bacterial characteristics. Research findings from one region might not be generalisable to other regions.
FUNDING
The National Institutes of Health.
Topics: Anti-Bacterial Agents; Bacteremia; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Cohort Studies; Humans; Klebsiella Infections; Klebsiella pneumoniae; Prospective Studies; Respiratory Sounds
PubMed: 34767753
DOI: 10.1016/S1473-3099(21)00399-6 -
Clinical Infectious Diseases : An... Feb 2023Next-generation sequencing (NGS) is increasingly used for periprosthetic joint infection (PJI) diagnosis, but its clinical utility is poorly defined. Shotgun metagenomic...
BACKGROUND
Next-generation sequencing (NGS) is increasingly used for periprosthetic joint infection (PJI) diagnosis, but its clinical utility is poorly defined. Shotgun metagenomic sequencing (sNGS) has been reported to identify PJI pathogens undetected by culture in sonicate fluid. However, sNGS is complex and costly. Here, 16S ribosomal RNA (rRNA) gene-based targeted metagenomic sequencing (tNGS) was compared to sNGS of sonicate fluid for microbial detection and identification in patients with total hip arthroplasty (THA) and total knee arthroplasty (TKA) failure.
METHODS
A convenience sample of sonicate fluids derived from patients who had undergone THA or TKA removal, enriched with culture negative PJI cases, was tested. Samples had been previously tested by sNGS. For tNGS, samples were extracted, amplified by polymerase chain reaction targeting the V1 to V3 regions of the 16S rRNA gene, and sequenced on an Illumina MiSeq.
RESULTS
A total of 395 sonicate fluids, including 208 from subjects with PJI, were studied. Compared with sonicate fluid culture, tNGS had higher positive percent agreement (72.1 vs 52.9%, P < .001), detecting potential pathogens in 48.0% of culture-negative PJIs. There was no difference between the positive percent agreement of tNGS (72.1%) and sNGS (73.1%, P = .83).
CONCLUSIONS
16S rRNA gene-based tNGS is a potential diagnostic tool for PJI pathogen identification in sonicate fluid from failed THAs and TKAs in culture-negative cases, with similar performance characteristics to sNGS.
Topics: Humans; Prosthesis-Related Infections; RNA, Ribosomal, 16S; Sensitivity and Specificity; Arthritis, Infectious; Arthroplasty, Replacement, Knee; Arthroplasty, Replacement, Hip
PubMed: 35944127
DOI: 10.1093/cid/ciac646 -
Toxins Sep 2017Adenylate cyclase-hemolysin toxin is secreted and produced by three classical species of the genus : , and . This toxin has several properties such as: (i) adenylate... (Review)
Review
Adenylate cyclase-hemolysin toxin is secreted and produced by three classical species of the genus : , and . This toxin has several properties such as: (i) adenylate cyclase activity, enhanced after interaction with the eukaryotic protein, calmodulin; (ii) a pore-forming activity; (iii) an invasive activity. It plays an important role in the pathogenesis of these species responsible for whooping cough in humans or persistent respiratory infections in mammals, by modulating host immune responses. In contrast with other toxins or adhesins, lack of (or very low polymorphism) is observed in the structural gene encoding this toxin, supporting its importance as well as a potential role as a vaccine antigen against whooping cough. In this article, an overview of the investigations undertaken on this toxin is presented.
Topics: Adenylate Cyclase Toxin; Animals; Bordetella; Humans; Respiratory Tract Infections; Virulence Factors, Bordetella; Whooping Cough
PubMed: 28892012
DOI: 10.3390/toxins9090277 -
Frontiers in Cellular and Infection... 2022A variety of bacteria have evolved the ability to interact with environmental phagocytic predators such as amoebae, which may have facilitated their subsequent...
A variety of bacteria have evolved the ability to interact with environmental phagocytic predators such as amoebae, which may have facilitated their subsequent interactions with phagocytes in animal hosts. Our recent study found that the animal pathogen can evade predation by the common soil amoeba , survive within, and hijack its complex life cycle as a propagation and dissemination vector. However, it is uncertain whether the mechanisms allowing interactions with predatory amoebae are conserved among species, because divergence, evolution, and adaptation to different hosts and ecological niches was accompanied by acquisition and loss of many genes. Here we tested 9 diverse species in three assays representing distinct aspects of their interactions with . Several human and animal pathogens retained the abilities to survive within single-celled amoeba, to inhibit amoebic plaque expansion, and to translocate with amoebae to the fruiting body and disseminate along with the fruiting body. In contrast, these abilities were partly degraded for the bird pathogen , and for the human-restricted species and . Interestingly, a different lineage of only known to infect sheep retained the ability to interact with , demonstrating that these abilities were lost in multiple lineages independently, correlating with niche specialization and recent rapid genome decay apparently mediated by insertion sequences. has been isolated sporadically from diverse human and environmental sources, has acquired insertion sequences, undergone genome decay and has also lost the ability to interact with amoebae, suggesting some specialization to some unknown niche. A genome-wide association study (GWAS) identified a set of genes that are potentially associated with the ability to interact with . These results suggest that massive gene loss associated with specialization of some species to a closed life cycle in a particular host was repeatedly and independently accompanied by loss of the ability to interact with amoebae in an environmental niche.
Topics: Amoeba; Animals; Bordetella; Bordetella bronchiseptica; Dictyostelium; Genome-Wide Association Study; Sheep
PubMed: 35223538
DOI: 10.3389/fcimb.2022.798317