Nontypeable<i>Haemophilus influenzae</i>and chronic obstructive pulmonary disease: a review for clinicians

Sriram, Krishna; Cox, Amanda J.; Clancy, Robert; Slack, Mary P. E.; Cripps, Allan W.

doi:10.1080/1040841x.2017.1329274

Cited by 39 publications

(34 citation statements)

References 186 publications

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“…While nontypeable Haemophilus influenzae (NTHi) is a common commensal of the human nasopharynx, this bacterium is also associated with a spectrum of diseases including otitis media and sinusitis, as well as hospital-and community-acquired pneumonia [1]. In addition, NTHi is the most common bacterial cause of chronic obstructive pulmonary disease (COPD) exacerbations [2][3][4]. NTHi has developed mechanisms to thrive in the hostile environment of different anatomical regions, such as the middle ear, upper and lower respiratory tracts, blood and the meninges [5].…”

Section: Introductionmentioning

confidence: 99%

Whole-genome analyses reveal gene content differences between nontypeable Haemophilus influenzae isolates from chronic obstructive pulmonary disease compared to other clinical phenotypes

Leong

Harkness

et al. 2020

Microbial Genomics

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Nontypeable Haemophilus influenzae (NTHi) colonizes human upper respiratory airways and plays a key role in the course and pathogenesis of acute exacerbations of chronic obstructive pulmonary disease (COPD). Currently, it is not possible to distinguish COPD isolates of NTHi from other clinical isolates of NTHi using conventional genotyping methods. Here, we analysed the core and accessory genome of 568 NTHi isolates, including 40 newly sequenced isolates, to look for genetic distinctions between NTHi isolates from COPD with respect to other illnesses, including otitis media, meningitis and pneumonia. Phylogenies based on polymorphic sites in the core-genome did not show discrimination between NTHi strains collected from different clinical phenotypes. However, pan-genome-wide association studies identified 79 unique NTHi accessory genes that were significantly associated with COPD. Furthermore, many of the COPD-related NTHi genes have known or predicted roles in virulence, transmembrane transport of metal ions and nutrients, cellular respiration and maintenance of redox homeostasis. This indicates that specific genes may be required by NTHi for its survival or virulence in the COPD lung. These results advance our understanding of the pathogenesis of NTHi infection in COPD lungs.

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Section: Introductionmentioning

confidence: 99%

Whole-genome analyses reveal gene content differences between nontypeable Haemophilus influenzae isolates from chronic obstructive pulmonary disease compared to other clinical phenotypes

Leong

Harkness

et al. 2020

Microbial Genomics

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“…There are currently no effective vaccination strategies for the prevention of NTHi infections, and treatment has been complicated by the rapid development of antibiotic resistance to first-and second-line antibiotics. Resistance is predominantly mediated by β-lactamase production [7]; however, the emergence and spread of β-lactamase-negative, ampicillin-resistant strains in many regions of the world is of substantial concern with treatment failure also being reported in response to macrolides [8][9][10] and fluoroquinolones [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

In Vitro Anti-NTHi Activity of Haemophilin-Producing Strains of Haemophilus haemolyticus

et al. 2020

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Nontypeable Haemophilus influenzae (NTHi) is a leading causative organism of opportunistic respiratory tract infections. However, there are currently no effective vaccination strategies, and existing treatments are compromised by antibiotic resistance. We previously characterized Haemophilus haemolyticus (Hh) strains capable of producing haemophilin (HPL), a heme-binding protein that restricts NTHi growth by limiting its access to an essential growth factor, heme. Thus, these strains may have utility as a probiotic therapy against NTHi infection by limiting colonization, migration and subsequent infection in susceptible individuals. Here, we assess the preliminary feasibility of this approach by direct in vitro competition assays between NTHi and Hh strains with varying capacity to produce HPL. Subsequent changes in NTHi growth rate and fitness, in conjunction with HPL expression analysis, were employed to assess the NTHi-inhibitory capacity of Hh strains. HPL-producing strains of Hh not only outcompeted NTHi during short-term and extended co-culture, but also demonstrated a growth advantage compared with Hh strains unable to produce the protein. Additionally, HPL expression levels during competition correlated with the NTHi-inhibitory phenotype. HPL-producing strains of Hh demonstrate significant probiotic potential against NTHi colonization in the upper respiratory tract, however, further investigations are warranted to demonstrate a range of other characteristics that would support the eventual development of a probiotic.

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“…It is characterized as serotype a to f based on polysaccharide capsule antigens and lack of a capsule are identified as nontypeable (NTHi). NTHi has been the most prevalent cause of community-acquired pneumonia and exacerbation of chronic obstructive pulmonary disease (COPD) (3,4). In addition, invasive diseases caused by NTHi are emerging globally and is predisposed by age and coexisting conditions (5).…”

Section: Introductionmentioning

confidence: 99%

Molecular Epidemiology and Antimicrobial Resistance of Haemophilus influenzae in Adult Patients in Shanghai, China

Xiao

et al. 2020

Front. Public Health

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Background: The serotype and antimicrobial resistance of Haemophilus influenzae in adult patients have changed due to the application of antimicrobials and H. influenzae type b (Hib) vaccine worldwide. However, the epidemiologic characteristics of H. influenzae in Shanghai are still unavailable. Objective: To determine the serotype distribution, antimicrobial resistance and multilocus sequence type (MLST) of H. influenzae in adult patients in Shanghai. Methods: A total of 51 clinical isolates from adult patients were consecutively collected. Serotypes were determined according to specific capsule gene, bexA, amplified by PCR. Antimicrobial susceptibility test was carried out by the broth microdilution method. β-lactamase production was detected by cefinase disk and the ftsI gene were amplified and sequenced to determine the penicillin binding protein 3 (PBP3) mutation. Molecular epidemiology was performed by MLST analyses. Results: All isolates studied were nontypeable H. influenzae (NTHi) and three of them (5.88%) caused invasive infection. The resistant rates of ampicillin and trimethoprim/sulfamethoxazole were both 45.10%. One third of these isolates produced TEM-1 type β-lactamase and 11.76% were β-lactamase negative ampicillin resistant strains (BLNAR). The PBP3 mutation was detected in 74.51% of the isolates, of which 12 belonged to group III. A total of 36 sequence types (STs) were identified among all isolates. Four isolates of ST103 (7.84%) all produced β-lactamase without mutation of PBP3. Conclusion: H. influenzae infections among adults in Shanghai are predominately caused by NTHi with genetic diversity among adult patients. The prevalence of both β-lactamase production and PBP3 mutation may contribute to high ampicillin resistance rate in Shanghai.

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NontypeableHaemophilus influenzaeand chronic obstructive pulmonary disease: a review for clinicians

Cited by 39 publications

References 186 publications

Whole-genome analyses reveal gene content differences between nontypeable Haemophilus influenzae isolates from chronic obstructive pulmonary disease compared to other clinical phenotypes

Whole-genome analyses reveal gene content differences between nontypeable Haemophilus influenzae isolates from chronic obstructive pulmonary disease compared to other clinical phenotypes

In Vitro Anti-NTHi Activity of Haemophilin-Producing Strains of Haemophilus haemolyticus

Molecular Epidemiology and Antimicrobial Resistance of Haemophilus influenzae in Adult Patients in Shanghai, China

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