Monoclonal antibodies that target extracellular DNABII proteins or the type IV pilus of nontypeable Haemophilus influenzae (NTHI) worked additively to disrupt 2-genera biofilms

Jurcisek, Joseph A.; Hofer, Llwyatt K; Goodman, Steven D.

doi:10.1016/j.bioflm.2022.100096

Cited by 12 publications

(10 citation statements)

References 70 publications

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“…Studies have shown that two monoclonal antibodies targeting a subunit specific to NTHI (PilA) and to DNABII (common structural protein in bacteria) led to a breakdown of the biofilm, allowing for more effectiveness of antibiotics. Further research should also investigate the role of using monoclonal antibodies, as it may allow for early eradication and prevention of serious infections such as meningitis seen in our case [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Changing Landscape of Haemophilus influenzae Meningitis and Implication on Public Health

Allonce,

Ahsan,

Browne

et al. 2024

Case Reports in Infectious Diseases

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Haemophilus influenzae (H. influenzae) has evolved as a prominent pathogen, with nontypeable strains (NTHi) emerging as a leading cause of invasive disease, particularly among the elderly. Since the introduction of Haemophilus influenzae B (Hib) vaccine, invasive infection has shifted from children with Hib to the elderly with NTHi. NTHi affects those primarily with predisposing factors such as an immunocompromised state, CSF leakage, or ENT infections. We present two cases that emphasize the shift of invasive infection, risk factors, and elevated intracranial pressure (ICP) as a complication. Case 1. A 75-year-old female with a sudden onset of weakness and respiratory symptoms deteriorated rapidly. Imaging revealed mastoid effusion and ventriculitis, likely originating from otomastoiditis. Lumber puncture confirmed NTHi. ICU course complicated by elevated ICP prompted repeat lumbar puncture. The patient recovered after 8 days but not near baseline. Case 2. A 50-year-old female with altered mental status, headache, and ear pain exhibited signs of pansinusitis and pseudotumor cerebri. Elevated ICP was evident upon lumbar puncture, and NTHi was isolated in CSF and blood cultures. MRI of the brain showed prominent optic nerve sheaths and transverse sinus arachnoid granulations’ concern for underlying pseudotumor cerebri. Repeat lumbar puncture or ventricular drainage was deferred after discussion with neurosurgery. Diabetes was identified as a comorbidity. The patient’s condition improved after 14 days of antibiotics and dexamethasone. These cases emphasize the shifting landscape of H. influenzae meningitis, primarily driven by NTHi, especially among the elderly. Although NTHi infections were considered less invasive, recent epidemiology review indicated it as the leading cause of H. influenzae meningitis. With the increasing prevalence of NTHi and its increase in invasive patterns, it is crucial to implement vaccination strategies and develop new vaccines targeting NTHi.

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Section: Discussionmentioning

confidence: 99%

Changing Landscape of Haemophilus influenzae Meningitis and Implication on Public Health

Allonce,

Ahsan,

Browne

et al. 2024

Case Reports in Infectious Diseases

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“…Bacterial resistance to antibiotics can be natural or acquired [40]: natural resistance occurs when bacteria are resistant a priori, and it may be intrinsic (resistance-associated genes always expressed in the species independently from exposure to antibiotics), or induced (resistance genes are naturally occurring in bacteria, but are only expressed to resistance levels after antibiotic exposure) [40]; acquired resistance occurs by acquisition of genetic material through horizontal gene transfer or by mutations that bacteria accumulate in their genome [38].…”

Section: Vaccines and Mabs As Alternatives To Antibiotics In Fighting...mentioning

confidence: 99%

Vaccines and Monoclonal Antibodies as Alternative Strategies to Antibiotics to Fight Antimicrobial Resistance

La Guidara,

Adamo,

Sala

et al. 2024

IJMS

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Antimicrobial resistance (AMR) is one of the most critical threats to global public health in the 21st century, causing a large number of deaths every year in both high-income and low- and middle-income countries. Vaccines and monoclonal antibodies can be exploited to prevent and treat diseases caused by AMR pathogens, thereby reducing antibiotic use and decreasing selective pressure that favors the emergence of resistant strains. Here, differences in the mechanism of action and resistance of vaccines and monoclonal antibodies compared to antibiotics are discussed. The state of the art for vaccine technologies and monoclonal antibodies are reviewed, with a particular focus on approaches validated in clinical studies. By underscoring the scope and limitations of the different emerging technologies, this review points out the complementary of vaccines and monoclonal antibodies in fighting AMR. Gaps in antigen discovery for some pathogens, as well as challenges associated with the clinical development of these therapies against AMR pathogens, are highlighted.

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“…mAbs are viewed as a treatment option for high-risk individuals for whom vaccination is not an option and passive administration of mAbs could have a major effect on P. aeruginosa pathogenesis by conferring immediate protection, thus complementing the effect of prophylactic vaccines. For example, to overcome canonical antimicrobial resistance of biofilm-resident bacteria, monoclonal antibodies that can release P. aeruginosa and its common co-pathogens from the protective biofilm for subsequent killing by antibiotics have been developed [ 145 ]. Indeed, monoclonal antibodies directed against DNABII protein epitopes or targeting type IV pilus from the respiratory tract pathogen Haemophilus influenzae significantly impaired biofilms of P. aeruginosa and related respiratory tract pathogens ( Burkholderia cenocepacia , Staphylococcus aureus , Streptococcus pneumoniae or Moraxella catarrhalis [ 145 ]).…”

Section: Main Textmentioning

confidence: 99%

“…For example, to overcome canonical antimicrobial resistance of biofilm-resident bacteria, monoclonal antibodies that can release P. aeruginosa and its common co-pathogens from the protective biofilm for subsequent killing by antibiotics have been developed [ 145 ]. Indeed, monoclonal antibodies directed against DNABII protein epitopes or targeting type IV pilus from the respiratory tract pathogen Haemophilus influenzae significantly impaired biofilms of P. aeruginosa and related respiratory tract pathogens ( Burkholderia cenocepacia , Staphylococcus aureus , Streptococcus pneumoniae or Moraxella catarrhalis [ 145 ]). Among the mAbs candidates that have been examined, chicken egg yolk immunoglobulins IgY antibodies, have drawn a special interest in passive immunization due to a wide range of features encompassing the absence of immunological cross-reactivity with mammalian IgG and the complement system, high levels of antigen-specific production yield without disease resistance, and ability to facilitate immunization methods without stress in human [ 146 , 147 ].…”

Section: Main Textmentioning

confidence: 99%

Recent advances in therapeutic targets identification and development of treatment strategies towards Pseudomonas aeruginosa infections

et al. 2023

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The opportunistic human pathogen Pseudomonas aeruginosa is the causal agent of a wide variety of infections. This non-fermentative Gram-negative bacillus can colonize zones where the skin barrier is weakened, such as wounds or burns. It also causes infections of the urinary tract, respiratory system or bloodstream. P. aeruginosa infections are common in hospitalized patients for which multidrug-resistant, respectively extensively drug-resistant isolates can be a strong contributor to a high rate of in-hospital mortality. Moreover, chronic respiratory system infections of cystic fibrosis patients are especially concerning, since very tedious to treat. P. aeruginosa exploits diverse cell-associated and secreted virulence factors, which play essential roles in its pathogenesis. Those factors encompass carbohydrate-binding proteins, quorum sensing that monitor the production of extracellular products, genes conferring extensive drug resistance, and a secretion system to deliver effectors to kill competitors or subvert host essential functions. In this article, we highlight recent advances in the understanding of P. aeruginosa pathogenicity and virulence as well as efforts for the identification of new drug targets and the development of new therapeutic strategies against P. aeruginosa infections. These recent advances provide innovative and promising strategies to circumvent infection caused by this important human pathogen.

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Monoclonal antibodies that target extracellular DNABII proteins or the type IV pilus of nontypeable Haemophilus influenzae (NTHI) worked additively to disrupt 2-genera biofilms

Cited by 12 publications

References 70 publications

Changing Landscape of Haemophilus influenzae Meningitis and Implication on Public Health

Changing Landscape of Haemophilus influenzae Meningitis and Implication on Public Health

Vaccines and Monoclonal Antibodies as Alternative Strategies to Antibiotics to Fight Antimicrobial Resistance

Recent advances in therapeutic targets identification and development of treatment strategies towards Pseudomonas aeruginosa infections

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