Limits...
Benzalkonium tolerance genes and outcome in Listeria monocytogenes meningitis

View Article: PubMed Central - PubMed

ABSTRACT

Objectives: Listeria monocytogenes is a food-borne pathogen that can cause meningitis. The listerial genotype ST6 has been linked to increasing rates of unfavourable outcome over time. We investigated listerial genetic variation and the relation with clinical outcome in meningitis.

Methods: We sequenced 96 isolates from adults with listerial meningitis included in two prospective nationwide cohort studies by whole genome sequencing, and evaluated associations between bacterial genetic variation and clinical outcome. We validated these results by screening listerial genotypes of 445 cerebrospinal fluid and blood isolates from patients over a 30-year period from the Dutch national surveillance cohort.

Results: We identified a bacteriophage, phiLMST6 co-occurring with a novel plasmid, pLMST6, in ST6 isolates to be associated with unfavourable outcome in patients (p 2.83e-05). The plasmid carries a benzalkonium chloride tolerance gene, emrC, conferring decreased susceptibility to disinfectants used in the food-processing industry. Isolates harbouring emrC were growth inhibited at higher levels of benzalkonium chloride (median 60 mg/L versus 15 mg/L; p <0.001), and had higher MICs for amoxicillin and gentamicin compared with isolates without emrC (both p <0.001). Transformation of pLMST6 into naive strains led to benzalkonium chloride tolerance and higher MICs for gentamicin.

Conclusions: These results show that a novel plasmid, carrying the efflux transporter emrC, is associated with increased incidence of ST6 listerial meningitis in the Netherlands. Suggesting increased disease severity, our findings warrant consideration of disinfectants used in the food-processing industry that select for resistance mechanisms and may, inadvertently, lead to increased risk of poor disease outcome.

No MeSH data available.


Related in: MedlinePlus

Absolute number of Listeria monocytogenes meningitis cases for the largest multi locus sequence type groups from 1985 to 2014 in The Netherlands. The absolute number of cases per listerial multi-locus sequence type causing meningitis in the Netherlands is shown for six time intervals. The number of listeria meningitis cases did not vary significantly over the time intervals. Data for the five most common sequence types (STs) is shown. Remaining STs are clustered in the category ‘other STs’. In the time interval 1985–1989, ST1 and ST2 were the dominant STs. In the following years, ST1 and ST2 cases decreased whereas ST6 cases increased. In 2010–2014, ST6 caused disease in most cases, followed by ST1 and ST2. The number of ST6 cases increased significantly over the years (Mann–Whitney U test, p <0.001). ST6 is coloured cyan, ST1 is yellow, ST2 is green, ST3 is purple, ST8 is blue, and other STs are red.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5392494&req=5

fig3: Absolute number of Listeria monocytogenes meningitis cases for the largest multi locus sequence type groups from 1985 to 2014 in The Netherlands. The absolute number of cases per listerial multi-locus sequence type causing meningitis in the Netherlands is shown for six time intervals. The number of listeria meningitis cases did not vary significantly over the time intervals. Data for the five most common sequence types (STs) is shown. Remaining STs are clustered in the category ‘other STs’. In the time interval 1985–1989, ST1 and ST2 were the dominant STs. In the following years, ST1 and ST2 cases decreased whereas ST6 cases increased. In 2010–2014, ST6 caused disease in most cases, followed by ST1 and ST2. The number of ST6 cases increased significantly over the years (Mann–Whitney U test, p <0.001). ST6 is coloured cyan, ST1 is yellow, ST2 is green, ST3 is purple, ST8 is blue, and other STs are red.

Mentions: The reference laboratory received 1084 listerial isolates between 1 January 1985 and 1 January 2015; 371 of these isolates were from CSF, the remaining 713 were isolated from blood. For this study, we analysed all 371 CSF isolates and a randomly selected set of 74 blood isolates. Multi-locus sequence typing showed 62 different sequence types; most common were ST2 (in 102 isolates; 23%), ST1 (68; 15%), and ST6 (44; 10%). The proportion of ST6 cases increased significantly over the years (Fig. 3; Mann–Whitney U test, p <0.001), and the 5-year interval of ST6 emergence in this data set was in line with the inferred date from Bayesian dating for emergence of the most recent common ancestor to isolates carrying pLMST6 containing emrC.


Benzalkonium tolerance genes and outcome in Listeria monocytogenes meningitis
Absolute number of Listeria monocytogenes meningitis cases for the largest multi locus sequence type groups from 1985 to 2014 in The Netherlands. The absolute number of cases per listerial multi-locus sequence type causing meningitis in the Netherlands is shown for six time intervals. The number of listeria meningitis cases did not vary significantly over the time intervals. Data for the five most common sequence types (STs) is shown. Remaining STs are clustered in the category ‘other STs’. In the time interval 1985–1989, ST1 and ST2 were the dominant STs. In the following years, ST1 and ST2 cases decreased whereas ST6 cases increased. In 2010–2014, ST6 caused disease in most cases, followed by ST1 and ST2. The number of ST6 cases increased significantly over the years (Mann–Whitney U test, p <0.001). ST6 is coloured cyan, ST1 is yellow, ST2 is green, ST3 is purple, ST8 is blue, and other STs are red.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5392494&req=5

fig3: Absolute number of Listeria monocytogenes meningitis cases for the largest multi locus sequence type groups from 1985 to 2014 in The Netherlands. The absolute number of cases per listerial multi-locus sequence type causing meningitis in the Netherlands is shown for six time intervals. The number of listeria meningitis cases did not vary significantly over the time intervals. Data for the five most common sequence types (STs) is shown. Remaining STs are clustered in the category ‘other STs’. In the time interval 1985–1989, ST1 and ST2 were the dominant STs. In the following years, ST1 and ST2 cases decreased whereas ST6 cases increased. In 2010–2014, ST6 caused disease in most cases, followed by ST1 and ST2. The number of ST6 cases increased significantly over the years (Mann–Whitney U test, p <0.001). ST6 is coloured cyan, ST1 is yellow, ST2 is green, ST3 is purple, ST8 is blue, and other STs are red.
Mentions: The reference laboratory received 1084 listerial isolates between 1 January 1985 and 1 January 2015; 371 of these isolates were from CSF, the remaining 713 were isolated from blood. For this study, we analysed all 371 CSF isolates and a randomly selected set of 74 blood isolates. Multi-locus sequence typing showed 62 different sequence types; most common were ST2 (in 102 isolates; 23%), ST1 (68; 15%), and ST6 (44; 10%). The proportion of ST6 cases increased significantly over the years (Fig. 3; Mann–Whitney U test, p <0.001), and the 5-year interval of ST6 emergence in this data set was in line with the inferred date from Bayesian dating for emergence of the most recent common ancestor to isolates carrying pLMST6 containing emrC.

View Article: PubMed Central - PubMed

ABSTRACT

Objectives: Listeria monocytogenes is a food-borne pathogen that can cause meningitis. The listerial genotype ST6 has been linked to increasing rates of unfavourable outcome over time. We investigated listerial genetic variation and the relation with clinical outcome in meningitis.

Methods: We sequenced 96 isolates from adults with listerial meningitis included in two prospective nationwide cohort studies by whole genome sequencing, and evaluated associations between bacterial genetic variation and clinical outcome. We validated these results by screening listerial genotypes of 445 cerebrospinal fluid and blood isolates from patients over a 30-year period from the Dutch national surveillance cohort.

Results: We identified a bacteriophage, phiLMST6 co-occurring with a novel plasmid, pLMST6, in ST6 isolates to be associated with unfavourable outcome in patients (p 2.83e-05). The plasmid carries a benzalkonium chloride tolerance gene, emrC, conferring decreased susceptibility to disinfectants used in the food-processing industry. Isolates harbouring emrC were growth inhibited at higher levels of benzalkonium chloride (median 60&nbsp;mg/L versus 15&nbsp;mg/L; p &lt;0.001), and had higher MICs for amoxicillin and gentamicin compared with isolates without emrC (both p &lt;0.001). Transformation of pLMST6 into naive strains led to benzalkonium chloride tolerance and higher MICs for gentamicin.

Conclusions: These results show that a novel plasmid, carrying the efflux transporter emrC, is associated with increased incidence of ST6 listerial meningitis in the Netherlands. Suggesting increased disease severity, our findings warrant consideration of disinfectants used in the food-processing industry that select for resistance mechanisms and may, inadvertently, lead to increased risk of poor disease outcome.

No MeSH data available.


Related in: MedlinePlus